Is ACTB p.Pro32= (c.96C>T) pathogenic?

ACTB p.Pro32= (c.96C>T) is classified Benign/Likely benign in ACTB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0634%, amr); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Pro32= (c.96C>T)?

ACTB p.Pro32= (c.96C>T) is associated with Baraitser-Winter syndrome 1, developmental malformations-deafness-dystonia syndrome (ClinVar).

How common is ACTB p.Pro32= (c.96C>T) in the general population?

ACTB p.Pro32= (c.96C>T) is ultra-rare (popmax 0.0634%, amr) (gnomAD).

ACTB p.Pro32=

c.96C>T · rs755754152 · VCV502223

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0634%, amr)

Conditions

Baraitser-Winter syndrome 1

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 -5	GERP -4.2
Overall
CADD	6.962	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0634% Admixed American · 38/59,944 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0418%

Overall 0.00248% 40/1,611,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0634%	1,577
African / African-American	0.00134%	74,906
European (non-Finnish)	8.48e-05%	1,179,486

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.Pro32=
Coding: c.96C>T
MANE Select: NM_001101
dbSNP: rs755754152
Type: single nucleotide variant
Location: chr7:5529562 (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 syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental malformations-deafness-dystonia syndrome

Similar variants

ACTB p.Pro32Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro32 (accessed [today's date]).

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