HEXA p.Ser302=
c.906C>T · rs765612435 · VCV699587
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, eas)
Conditions
2
Inborn genetic diseases
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 1.7 | GERP -2.5, phastCons 0.96 |
| Overall | ||
| CADD | 9.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
East Asian · 8/44,898 alleles
Filtering AF
0.00883%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.000682%
11/1,613,646 alleles · ultra-rare
exomes 8/1,461,474 · genomes 3/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0178% | 5,612 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| European (non-Finnish) | 8.48e-05% | 1,179,660 |
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
- HEXA
- Protein
- p.Ser302=
- Coding
- c.906C>T
- MANE Select
- NM_000520
- dbSNP
- rs765612435
- Type
- single nucleotide variant
- Location
- chr15:72349159 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.62 · 2 PDB
- Residue 302
- an α-helix
Similar variants
- HEXA c.1073+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HEXA c.1330+1G>A Pathogenic ★★ same condition
- HEXA c.1330+2T>C Pathogenic ★★ same condition
- HEXA c.1421+1G>C Pathogenic ★★ same condition
- HEXA c.1421+1G>T Pathogenic/Likely pathogenic ★★ same condition
- HEXA c.1526+1G>T Pathogenic/Likely pathogenic ★★ same condition
- HEXA c.253+1G>A Likely pathogenic ★★ same condition
- HEXA c.254-1G>C 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/hexa-p-ser302 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown