HECW2 p.Ser481=
c.1443C>T · VCV4959264
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, 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 2.3 | GERP -1.1, phastCons 0.97 |
| Overall | ||
| CADD | 5.502 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,924 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00124%
20/1,613,808 alleles · very rare
exomes 15/1,461,620 · genomes 5/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,731 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.00127% | 78,664 |
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
- HECW2
- Protein
- p.Ser481=
- Coding
- c.1443C>T
- MANE Select
- NM_001348768
- Type
- single nucleotide variant
- Location
- chr2:196319447 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 62.07 · 2 PDB
Similar variants
- HECW2 p.Arg1191Gln Pathogenic ★★ same type
- HECW2 p.Arg1191Trp Likely pathogenic ★★ same type
- HECW2 p.Arg1330Trp Pathogenic ★★ same type
- HECW2 p.Arg1495Ser Pathogenic/Likely pathogenic ★★ same type
- HECW2 p.Asn1199Lys Pathogenic/Likely pathogenic ★★ same type
- HECW2 p.Asn1199Ser Likely pathogenic ★★ ⚠ same type
- HECW2 p.Leu1448Ser Likely pathogenic ★★ same type
- HECW2 p.Ser1504Tyr Likely pathogenic ★★ 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/hecw2-p-ser481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown