HECW2 p.Ser596=
c.1788T>C · VCV4959257
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000682%, 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 -0.35 | GERP -0.8, phastCons 0.001 |
| Overall | ||
| CADD | 1.409 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000682%
European (non-Finnish) · 8/1,172,424 alleles
Filtering AF
0.000294%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000501%
8/1,598,392 alleles · very rare
exomes 8/1,446,068 · genomes 0/152,324 · 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.Ser596=
- Coding
- c.1788T>C
- MANE Select
- NM_001348768
- Type
- single nucleotide variant
- Location
- chr2:196319102 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 62.07 · 2 PDB
- Residue 596
- the 'disordered' 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-ser596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown