Is ACTG1 p.Pro264Ser (c.790C>T) pathogenic?

ACTG1 p.Pro264Ser (c.790C>T) is classified Uncertain significance in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.9719); Very rare (popmax 0.00333%, amr).

How common is ACTG1 p.Pro264Ser (c.790C>T) in the general population?

ACTG1 p.Pro264Ser (c.790C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ACTG1 p.Pro264Ser (c.790C>T)?

AlphaMissense predicts likely pathogenic (score 0.9719) — an in-silico prediction, not a clinical call.

ACTG1 p.Pro264Ser

c.790C>T · VCV3363734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9719	likely pathogenic
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.76, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 265 bp · p 0.016 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000205% 3/1,461,376 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,014
European (non-Finnish)	8.47e-05%	1,180,034

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: ACTG1
Protein: p.Pro264Ser
Coding: c.790C>T
MANE Select: NM_001614
Type: single nucleotide variant
Location: chr17:81511200 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 264: a UniProt-annotated variant site (in dfna20); an α-helix

Full ACTG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTG1 p.Pro264Leu Pathogenic ★★ same residue
ACTG1 p.Pro264= Likely benign ★ same residue
ACTG1 p.Ala135Val Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Ala204Gly Likely pathogenic ★★ same type
ACTG1 p.Arg183Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg183Trp Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg206Gln Pathogenic/Likely pathogenic ★★ same type
ACTG1 p.Arg210Cys 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/actg1-p-pro264ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown