HERC2 p.Glu751=
c.2253A>G · rs61754658 · VCV785478
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.39%, 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 -1.2 | phastCons 0.002 |
| Overall | ||
| CADD | 1.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.39%
African / African-American · 1,040/75,072 alleles
Filtering AF
1.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.29%
Overall
0.072%
1,162/1,614,248 alleles · low-frequency
exomes 560/1,461,894 · genomes 602/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.39% | 72 |
| Remaining individualsnot grpmax-eligible | 0.0896% | 1,116 |
| Admixed American | 0.085% | 1,177 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.00769% | 13,012 |
| European (non-Finnish) | 0.000508% | 196,673 |
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.Glu751=
- Coding
- c.2253A>G
- MANE Select
- NM_004667
- dbSNP
- rs61754658
- Type
- single nucleotide variant
- Location
- chr15:28260840 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Residue 751
- a β-strand
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-glu751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown