HERC1 p.Ala2000=
c.6000C>T · rs186236651 · VCV776910
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.826%, afr)
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 5.2 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 9.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.826%
African / African-American · 615/74,464 alleles
Filtering AF
0.772%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.75%
Overall
0.0409%
650/1,587,412 alleles · rare
exomes 279/1,435,170 · genomes 371/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.826% | 121 |
| Remaining individualsnot grpmax-eligible | 0.0374% | 2,677 |
| Middle Eastern | 0.0331% | 3,018 |
| Admixed American | 0.016% | 6,248 |
| European (non-Finnish) | 8.58e-05% | 1,165,564 |
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.Ala2000=
- Coding
- c.6000C>T
- MANE Select
- NM_003922
- dbSNP
- rs186236651
- Type
- single nucleotide variant
- Location
- chr15:63689637 (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-ala2000 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown