Is ACTB p.Gly343= (c.1029C>T) pathogenic?

ACTB p.Gly343= (c.1029C>T) is classified Likely benign in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Very rare (popmax 0.00223%, eas); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Gly343= (c.1029C>T)?

ACTB p.Gly343= (c.1029C>T) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Gly343= (c.1029C>T) in the general population?

ACTB p.Gly343= (c.1029C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ACTB p.Gly343=

c.1029C>T · VCV4752028

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 3	GERP 1.8, phastCons 1
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,776 alleles

Overall 6.84e-05% 1/1,461,654 alleles · very rare

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.Gly343=
Coding: c.1029C>T
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5527847 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 343: an α-helix

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.Gly343Asp Uncertain significance ★ ⚠ same residue
ACTB p.Gly343Ser 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-gly343 (accessed [today's date]).

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