Is ACTB p.Pro32Ser (c.94C>T) pathogenic?

ACTB p.Pro32Ser (c.94C>T) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-23). AlphaMissense: likely pathogenic (0.9746); Very rare (popmax 0.00134%, afr); Associated with Baraitser-Winter cerebrofrontofacial syndrome.

What condition is associated with ACTB p.Pro32Ser (c.94C>T)?

ACTB p.Pro32Ser (c.94C>T) is associated with Baraitser-Winter cerebrofrontofacial syndrome, Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Pro32Ser (c.94C>T) in the general population?

ACTB p.Pro32Ser (c.94C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ACTB p.Pro32Ser (c.94C>T)?

AlphaMissense predicts likely pathogenic (score 0.9746) — an in-silico prediction, not a clinical call.

ACTB p.Pro32Ser

c.94C>T · rs779839358 · VCV1309667

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Baraitser-Winter cerebrofrontofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.9746	likely pathogenic
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -15.27	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 289 bp · p 4.5e-15 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Overall 0.000124% 2/1,611,542 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,904
European (non-Finnish)	8.48e-05%	1,179,510

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: ACTB
Protein: p.Pro32Ser
Coding: c.94C>T
MANE Select: NM_001101
dbSNP: rs779839358
Type: single nucleotide variant
Location: chr7:5529564 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 32: a β-strand

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

Disease context

Baraitser-Winter cerebrofrontofacial syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baraitser-Winter syndrome 1

Similar variants

ACTB p.Pro32= Benign/Likely benign ★★ same residue
ACTB p.Pro32Arg Likely pathogenic ★ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Ala7Thr Likely pathogenic ★★ same condition
ACTB p.Arg147Cys Pathogenic ★★ same condition
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg196Cys Pathogenic ★★ same condition
ACTB p.Arg196His 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/actb-p-pro32ser (accessed [today's date]).

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