Is ACTB p.Asn252= (c.756T>C) pathogenic?

ACTB p.Asn252= (c.756T>C) is classified Likely benign in ACTB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-02). Ultra-rare (popmax 0.0194%, nfe); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Asn252= (c.756T>C)?

ACTB p.Asn252= (c.756T>C) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Asn252= (c.756T>C) in the general population?

ACTB p.Asn252= (c.756T>C) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

ACTB p.Asn252=

c.756T>C · rs774251900 · VCV1093330

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Conditions

Baraitser-Winter syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.6	GERP -3.7
Overall
CADD	0.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0194% European (non-Finnish) · 229/1,180,058 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0142% 230/1,614,074 alleles · ultra-rare exomes 224/1,461,824 · genomes 6/152,250 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,153
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Asn252=
Coding: c.756T>C
MANE Select: NM_001101
dbSNP: rs774251900
Type: single nucleotide variant
Location: chr7:5528327 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB

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

Similar variants

ACTB p.Asn252Asp Uncertain significance ★ ⚠ same residue
ACTB p.Asn252Ser Uncertain significance ★ ⚠ 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-asn252 (accessed [today's date]).

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