HFE p.Pro232=
c.696C>T · rs775728624 · VCV1079917
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, sas)
Conditions
1
hereditary hemochromatosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.1 | |
| Overall | ||
| CADD | 1.843 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
South Asian · 28/91,088 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00266%
43/1,614,198 alleles · ultra-rare
exomes 43/1,461,894 · genomes 0/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0307% | 3,253 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.00119% | 84,287 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- HFE
- Protein
- p.Pro232=
- Coding
- c.696C>T
- MANE Select
- NM_000410
- dbSNP
- rs775728624
- Type
- single nucleotide variant
- Location
- chr6:26092764 (GRCh38)
- Gene constraint
- LOEUF 1.037 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.62 · 2 PDB
- Residue 232
- the ig-like c1-type domain; a β-strand; the 'alpha-3' region
Similar variants
- HFE c.1006+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HFE c.616+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HFE c.616+1G>T Pathogenic ★★ same condition
- HFE c.76+2T>C Likely pathogenic ★★ same condition
- HFE p.Gln283Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
- HFE p.Glu298Ter Pathogenic/Likely pathogenic ★★ same condition
- HFE p.Leu183Pro Pathogenic/Likely pathogenic ★★ same condition
- HFE p.Lys254Ter Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hfe-p-pro232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown