HERC1 p.Arg262=
c.786A>G · rs2228515 · VCV1245846
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.76%, afr) — too common for a highly-penetrant pathogenic allele
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 -2.4 | GERP -3.4 |
| Overall | ||
| CADD | 4.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.76%
African / African-American · 5,074/75,026 alleles
Filtering AF
6.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.54%
Overall
1.78%
28,745/1,613,960 alleles · common
exomes 24,051/1,461,698 · genomes 4,694/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.76% | 15 |
| Ashkenazi Jewishnot grpmax-eligible | 3.86% | 26 |
| Middle Eastern | 3.45% | 29 |
| Amishnot grpmax-eligible | 2.3% | 43 |
| Finnishnot grpmax-eligible | 2.29% | 44 |
| Remaining individualsnot grpmax-eligible | 2.1% | 48 |
| South Asian | 1.81% | 55 |
| East Asian | 1.76% | 57 |
| Admixed American | 1.63% | 61 |
| European (non-Finnish) | 1.36% | 73 |
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
- HERC1
- Protein
- p.Arg262=
- Coding
- c.786A>G
- MANE Select
- NM_003922
- dbSNP
- rs2228515
- Type
- single nucleotide variant
- Location
- chr15:63774838 (GRCh38)
- Gene constraint
- LOEUF 0.33 · pLI 1.00 (gnomAD)
Similar variants
- HERC1 p.Arg2196Ter Pathogenic/Likely pathogenic ★★ same type
- HERC1 p.Arg3248Ter Pathogenic/Likely pathogenic ★★ same type
- HERC1 c.1026+6T>C Uncertain significance ★★ same type
- HERC1 c.12570+6G>A Uncertain significance ★★ same type
- HERC1 p.Ala1494Val Uncertain significance ★★ ⚠ same type
- HERC1 p.Ala2289Thr Uncertain significance ★★ ⚠ same type
- HERC1 p.Ala2539Thr Uncertain significance ★★ ⚠ same type
- HERC1 p.Ala276Glu Uncertain significance ★★ same type
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/herc1-p-arg262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown