HECW2 p.Pro920=
c.2760C>T · VCV4959238
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, nfe)
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 0.31 | GERP 0.54, phastCons 0.95 |
| Overall | ||
| CADD | 8.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
European (non-Finnish) · 26/1,179,488 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00161%
26/1,612,970 alleles · very rare
exomes 26/1,460,676 · genomes 0/152,294 · joint denominator
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.Pro920=
- Coding
- c.2760C>T
- MANE Select
- NM_001348768
- Type
- single nucleotide variant
- Location
- chr2:196306542 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 62.07 · 2 PDB
- Residue 920
- the 'interaction with tp73' region
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-pro920 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown