HERC2 p.Ser2986=
c.8958T>G · VCV4923696
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0388%, 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 -0.22 | phastCons 0.001 |
| Overall | ||
| CADD | 2.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0388%
African / African-American · 29/74,826 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0239%
Overall
0.00242%
39/1,609,728 alleles · ultra-rare
exomes 23/1,457,394 · genomes 16/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0388% | 2,580 |
| Middle Eastern | 0.0166% | 6,012 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,508 |
| Finnishnot grpmax-eligible | 0.00156% | 63,990 |
| European (non-Finnish) | 0.000594% | 168,274 |
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
- HERC2
- Protein
- p.Ser2986=
- Coding
- c.8958T>G
- MANE Select
- NM_004667
- Type
- single nucleotide variant
- Location
- chr15:28179203 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
Similar variants
- HERC2 c.4352-1G>A Likely pathogenic ★★ same type
- HERC2 p.Arg1376Ter Pathogenic/Likely pathogenic ★★ same type
- HERC2 c.12803-7C>A Uncertain significance ★★ same type
- HERC2 c.8451+8C>A Uncertain significance ★★ same type
- HERC2 p.Ala1253Thr Uncertain significance ★★ same type
- HERC2 p.Ala1454Thr Uncertain significance ★★ ⚠ same type
- HERC2 p.Ala200Val Uncertain significance ★★ ⚠ same type
- HERC2 p.Ala2331Val 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/herc2-p-ser2986 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown