Iron, a gene, and a common European spelling
Hereditary hemochromatosis is a condition in which the body absorbs too much iron. Over years, iron can deposit in the liver and other organs. The common genetic form in people of northern European ancestry involves the HFE gene.
Two spelling changes dominate the conversation: C282Y (rs1800562) and H63D (rs1799945). C282Y/C282Y is the genotype most associated with the classic recessive pattern. H63D is common and usually milder in effect. Neither rsID is a ferritin blood test.
Plenty of people with two C282Y copies never feel ill. Penetrance is incomplete. Men are diagnosed more often than women, in part because menstruation and pregnancy lose iron. A lookup tells you what the public record says about a site. A doctor measures iron.
- HFE: a gene involved in iron regulation
- C282Y / rs1800562: the classic risk spelling
- H63D / rs1799945: common, usually weaker on its own
HFE rs1800562 rs1799945 are the ids people type
HFE rs1800562 is p.Cys282Tyr, written C282Y in older papers. HFE rs1799945 is p.His63Asp, written H63D. Those two names dominate consumer-file questions about hereditary hemochromatosis.
Both are public dbSNP cluster ids. Anyone can look up the ClinVar assertion and the gnomAD frequency. That lookup does not measure iron. It does not diagnose hemochromatosis.
A third site, S65C (rs1800730), appears in some panels. This guide stays on the two rsIDs people actually type. Confirm live records before you memorize a forum table.
- rs1800562: HFE C282Y, p.Cys282Tyr, often NM_000410.4:c.845G>A
- rs1799945: HFE H63D, p.His63Asp, NM_000410.4:c.187C>G
- Personal iron status: ferritin and transferrin saturation, not a CLI
C282Y, H63D, and what the protein strings mean
C282Y and H63D are legacy protein nicknames. HGVS wants an accession. genome.sh will resolve the rsIDs without you typing c.845G>A, which is the safer path from a chip file.
Hereditary hemochromatosis type 1 is an HFE-related condition in clinical texts. Zygosity and compound heterozygosity are part of those texts. A single heterozygous chip call is not the clinical picture.
genome.sh will not tell you to donate blood. It will print the public record. Guidelines treat combinations and context. Do not reduce H63D to a forum rule.
If a report prints only C282Y, it skipped H63D. If it prints only H63D, it skipped C282Y. Query both rsIDs every time, then see which of them the file actually called.
Frequency in gnomAD is part of the story
These alleles are not ultra-rare in European-ancestry gnomAD. That is why they show up in chip reports. A high frequency does not delete the ClinVar record. A ClinVar label does not delete the frequency.
Read ClinVar vs gnomAD as two questions. ClinVar is submitted interpretation. gnomAD is how often the alternate allele appears among sequenced haplotypes.
Ancestry-group frequencies matter. Global AF can hide a common allele in one group. Open the gnomAD page when you need the full table.
If you only print ClinVar Pathogenic and hide AF, a reader will think the allele is vanishingly rare. If you only print AF and hide ClinVar, a reader will think frequency is a classification. Keep both columns in any table you ship.
Query both rsIDs locally and over HTTPS
Install genome-sh, then a standard or full database if you want frequency next to ClinVar. lite still answers the ClinVar half.
Query each rsID. JSON is for scripts. Human output is for one terminal. chr6:26090951 is the GRCh37 coordinate used in genome.sh docs for the H63D site; prefer the rsID so you do not mix assemblies.
The HTTP API has no key and rejects genome files. Use it for the public ids. Use the CLI for a local export.
cargo install genome-sh genome db install standard genome query rs1800562 genome query rs1799945 --format json curl -s https://api.genome.sh/v1/query/rs1800562 | jq . curl -s https://api.genome.sh/v1/query/rs1799945 | jq .
Chip coverage and the not-called rule
These two rsIDs are often on 23andMe and Ancestry arrays. Often is not always. Check the file.
If the row is missing, write not called. Do not infer homozygous reference. Do not infer C282Y-negative as a clinical sentence.
A consumer chip is still not a complete HFE test. Other HFE sites and other genes in iron overload are outside those two probes.
- Present and called: look up the public record, then read the two letters
- Present as no-call: not called
- Absent from the manifest: not called, not wild type
genome query rs1800562 --format json | jq . genome query rs1799945 --format json | jq . grep -w rs1800562 23andme.txt || echo not called grep -w rs1799945 23andme.txt || echo not called
Zygosity, chemistry, and what a CLI cannot measure
Clinical care for suspected hemochromatosis uses iron studies and, when appropriate, a validated genetic test interpreted by a clinician. Ferritin is not in the VCF.
Compound heterozygosity is a statement about two sites together. Looking up one rsID does not give you the pair. Query both, then see whether both were called.
Penetrance is incomplete in population studies. That is one reason a public Pathogenic or risk-style label is not a diagnosis of a person. genome.sh will not estimate penetrance for you.
Family history and biochemistry sit outside genome.sh. A homozygous chip call without iron studies is still not a clinic visit. Do not write treatment advice next to a CLI row.
Read ClinVar with gnomAD before you stop
Print significance, review status, and frequency. Keep conflicts if they exist. Then match the rsIDs to the local file.
If you annotate a VCF, genome annotate file.vcf.gz --format json still only sees called sites. Missing HFE rows stay not called.
This is informational lookup. It is not medical advice and not a treatment plan.
When an agent writes the PDF, it should query rs1800562 and rs1799945 separately, record not called independently, and refuse to diagnose. That is the whole local workflow for these two ids.
S65C, other iron genes, and why two probes are not a panel
rs1800730 (S65C) appears in some HFE discussions. This page focuses on rs1800562 and rs1799945 because those are the queries in the logs. If S65C is in your file, look it up the same way and still write not called when it is missing.
Other genes involved in iron overload will not be solved by two HFE SNPs. A consumer chip is not a hemochromatosis panel. genome query HFE returns a gene catalog, which is still not a personal result.
Use standard or full if you want gnomAD next to ClinVar. lite answers the ClinVar half. Cite genome db stats so a reader knows which snapshot you used.
genome query HFE --format json | jq 'length' genome query rs1800730 --format json curl -s https://api.genome.sh/v1/gnomad/rs1800562 | jq .
Questions
Which HFE variant is C282Y?
rs1800562. Confirm on the ClinVar or dbSNP record in a medical setting, not from memory. H63D is rs1799945.
What is rs1799945?
HFE p.His63Asp, commonly called H63D. It is a public identifier. It is not a ferritin result.
Is H63D pathogenic on its own?
ClinVar and guidelines treat combinations and context. Do not reduce it to a forum rule. Read the current ClinVar aggregate and review status.
Are rs1800562 and rs1799945 on 23andMe?
Often yes, but check the file. If the row is missing, it was not called. Missing is not wild type. A later chip version can differ from an older export you still have on disk.
How do I look up HFE rs1800562 from the command line?
cargo install genome-sh, genome db install standard, then genome query rs1800562. Add genome query rs1799945 for H63D.
Does a homozygous C282Y chip result diagnose hemochromatosis?
No. genome.sh will not diagnose hemochromatosis. Clinical care uses iron studies and an appropriate assay interpreted by a clinician. A CLI lookup does not measure ferritin and does not tell you to donate blood.
Should I use GRCh37 coordinates for HFE?
Prefer the rsID. chr6:26090951 is the GRCh37 example in genome.sh docs for H63D. Mixing assemblies maps the wrong base.
Is this medical advice?
No. genome.sh prints public annotations. It will not tell you to donate blood or to skip a clinician.