HEXA p.Ser4=
c.12C>T · rs774967373 · VCV1616846
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
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 2.5 | GERP -0.39, phastCons 0.79 |
| Overall | ||
| CADD | 10.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,180,024 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,890 alleles · very rare
exomes 4/1,461,552 · genomes 0/152,338 · 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
- HEXA
- Protein
- p.Ser4=
- Coding
- c.12C>T
- MANE Select
- NM_000520
- dbSNP
- rs774967373
- Type
- single nucleotide variant
- Location
- chr15:72375961 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.62 · 2 PDB
Similar variants
- HEXA p.Ser4Pro Uncertain significance ★★ ⚠ same residue
- HEXA p.Ser4_Arg5insSer Uncertain significance ★ same residue
- 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
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-ser4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown