HECW2 p.Pro332=
c.996A>G · rs10172730 · VCV788515
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.34%, afr)
Conditions
1
neurodevelopmental disorder with hypotonia, seizures, and absent language
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -4.6 |
| Overall | ||
| CADD | 2.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.34%
African / African-American · 2,484/74,312 alleles
Filtering AF
3.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.19%
Overall
0.186%
2,953/1,591,446 alleles · low-frequency
exomes 1,510/1,439,126 · genomes 1,443/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.34% | 30 |
| Admixed American | 0.282% | 354 |
| Remaining individualsnot grpmax-eligible | 0.264% | 379 |
| Middle Eastern | 0.168% | 596 |
| South Asian | 0.0191% | 5,242 |
| European (non-Finnish) | 0.01% | 9,961 |
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.Pro332=
- Coding
- c.996A>G
- MANE Select
- NM_001348768
- dbSNP
- rs10172730
- Type
- single nucleotide variant
- Location
- chr2:196319894 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 62.07 · 2 PDB
Similar variants
- HECW2 p.Arg1191Gln Pathogenic ★★ same condition
- HECW2 p.Arg1191Trp Likely pathogenic ★★ same condition
- HECW2 p.Arg1330Trp Pathogenic ★★ same condition
- HECW2 p.Arg1495Ser Pathogenic/Likely pathogenic ★★ same condition
- HECW2 p.Asn1199Lys Pathogenic/Likely pathogenic ★★ same condition
- HECW2 p.Asn1199Ser Likely pathogenic ★★ ⚠ same condition
- HECW2 p.Leu1448Ser Likely pathogenic ★★ same condition
- HECW2 p.Ser1504Tyr Likely pathogenic ★★ same condition
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-pro332 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown