ACTB p.Ser265Thr
c.793T>A · VCV4689977
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3934 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3934 | ambiguous |
|---|---|---|
| REVEL | 0.618 | indeterminate |
| SaProt | LLR -11.54 | damaging |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.11 | constrained · MANE · 1,149 bp · p 1.6e-51 · regional, not allelic |
| Overall | ||
| CADD | 24.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACTB
- Protein
- p.Ser265Thr
- Coding
- c.793T>A
- MANE Select
- NM_001101
- Type
- single nucleotide variant
- Location
- chr7:5528290 (GRCh38)
- Gene constraint
- LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.31 · 93 PDB
- Residue 265
- an α-helix
Similar variants
- ACTB p.Ser265= Likely benign ★★ same residue
- ACTB p.Ser265Ala Uncertain significance ★ ⚠ same residue
- ACTB p.Ala22Thr Likely pathogenic ★★ same type
- ACTB p.Ala7Thr Likely pathogenic ★★ same type
- ACTB p.Arg147Cys Pathogenic ★★ same type
- ACTB p.Arg183Trp Pathogenic ★★ same type
- ACTB p.Arg196Cys Pathogenic ★★ same type
- ACTB p.Arg196His Pathogenic ★★ 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/actb-p-ser265thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown