ACTL6A p.Thr331=
c.993A>G · rs146107398 · VCV2654292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 0.11 | GERP -4.4, phastCons 0.12 |
| Overall | ||
| CADD | 6.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,062 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0294%
Overall
0.00595%
96/1,614,000 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| African / African-American | 0.036% | 2,780 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,464 |
| Admixed American | 0.0133% | 7,501 |
| European (non-Finnish) | 0.00339% | 29,497 |
| South Asian | 0.0011% | 91,074 |
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
- ACTL6A
- Protein
- p.Thr331=
- Coding
- c.993A>G
- MANE Select
- NM_004301
- dbSNP
- rs146107398
- Type
- single nucleotide variant
- Location
- chr3:179581187 (GRCh38)
- Gene constraint
- LOEUF 0.186 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 92.04 · 31 PDB
- Residue 331
- an α-helix
Similar variants
- ACTL6A p.Arg389Trp Uncertain significance ★★ ⚠ same type
- ACTL6A p.Arg390Ser Uncertain significance ★★ ⚠ same type
- ACTL6A p.Asp339= Benign ★★ same type
- ACTL6A c.1209+1G>C Uncertain significance ★ same type
- ACTL6A c.477-1G>C Uncertain significance ★ same type
- ACTL6A c.477-2A>G Uncertain significance ★ same type
- ACTL6A c.572-4A>G Uncertain significance ★ same type
- ACTL6A c.768+1G>A 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/actl6a-p-thr331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown