Is ACTG1 p.Ser232Phe (c.695C>T) pathogenic?

ACTG1 p.Ser232Phe (c.695C>T) is classified Uncertain significance in ACTG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-03). AlphaMissense: likely pathogenic (0.6307); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ACTG1 p.Ser232Phe (c.695C>T)?

ACTG1 p.Ser232Phe (c.695C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACTG1 p.Ser232Phe (c.695C>T) in the general population?

ACTG1 p.Ser232Phe (c.695C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ACTG1 p.Ser232Phe (c.695C>T)?

AlphaMissense predicts likely pathogenic (score 0.6307) — an in-silico prediction, not a clinical call.

ACTG1 p.Ser232Phe

c.695C>T · rs1555666658 · VCV985276

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6307 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6307	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -13.04	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 265 bp · p 0.016 · regional, not allelic
Overall
CADD	25.9	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 0.0011% South Asian · 1/91,092 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,838 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,092
European (non-Finnish)	0.000678%	147,506

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.Ser232Phe
Coding: c.695C>T
MANE Select: NM_001614
dbSNP: rs1555666658
Type: single nucleotide variant
Location: chr17:81511295 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTG1 p.Ser232= Likely benign ★★ same residue
ACTG1 p.Arg335His Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Ala174Ser Uncertain significance ★★ ⚠ same condition
ACTG1 p.His87Tyr Uncertain significance ★★ ⚠ same condition
ACTG1 p.Ile192Val Uncertain significance ★★ ⚠ same condition
ACTG1 p.Thr126Ile Uncertain significance ★★ ⚠ same condition
ACTG1 p.Tyr143= Likely benign ★★ same condition
ACTG1 p.Tyr69Cys 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/actg1-p-ser232phe (accessed [today's date]).

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