ALDH4A1 p.Ser331=
c.993C>T · rs372376622 · VCV749341
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
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 0.12 | GERP -2.8, phastCons 0.68 |
| Overall | ||
| CADD | 8.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,844 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000993%
16/1,611,684 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00534% | 18,711 |
| South Asian | 0.0044% | 22,744 |
| European (non-Finnish) | 0.000678% | 147,453 |
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
- ALDH4A1
- Protein
- p.Ser331=
- Coding
- c.993C>T
- MANE Select
- NM_003748
- dbSNP
- rs372376622
- Type
- single nucleotide variant
- Location
- chr1:18877560 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.22 · 6 PDB
- Residue 331
- an α-helix
Similar variants
- ALDH4A1 c.866+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALDH4A1 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
- ALDH4A1 c.*272C>T Uncertain significance ★★ same type
- ALDH4A1 c.*646G>A Uncertain significance ★★ same type
- ALDH4A1 p.Ala162Thr Uncertain significance ★★ ⚠ same type
- ALDH4A1 p.Ala163Thr Uncertain significance ★★ ⚠ same type
- ALDH4A1 p.Ala220Pro Uncertain significance ★★ ⚠ same type
- ALDH4A1 p.Ala238Thr Uncertain significance ★★ ⚠ 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/aldh4a1-p-ser331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown