Is ACTB p.Ile341= (c.1023C>T) pathogenic?

ACTB p.Ile341= (c.1023C>T) is classified Benign in ACTB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.72%, afr); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Ile341= (c.1023C>T)?

ACTB p.Ile341= (c.1023C>T) is associated with Baraitser-Winter syndrome 1, developmental malformations-deafness-dystonia syndrome (ClinVar).

How common is ACTB p.Ile341= (c.1023C>T) in the general population?

ACTB p.Ile341= (c.1023C>T) is low-frequency (popmax 3.72%, afr) (gnomAD).

ACTB p.Ile341=

c.1023C>T · rs58704474 · VCV128263

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.72%, afr)

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 -1.8	GERP -3.7
Overall
CADD	6.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.72% African / African-American · 2,790/74,956 alleles

Filtering AF 3.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.56%

Overall 0.194% 3,133/1,613,878 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.72%	27
Remaining individualsnot grpmax-eligible	0.232%	431
Admixed American	0.21%	476
Middle Eastern	0.0495%	2,020
South Asian	0.00988%	10,119
European (non-Finnish)	0.005%	19,999
East Asian	0.00223%	44,850

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.Ile341=
Coding: c.1023C>T
MANE Select: NM_001101
dbSNP: rs58704474
Type: single nucleotide variant
Location: chr7:5527853 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 341: a UniProt-annotated variant site (in thc8; likely pathogenic); 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

Also linked: developmental malformations-deafness-dystonia syndrome

Similar variants

ACTB p.Ile341Val Likely pathogenic ★★ same residue
ACTB p.Ile341Leu 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-ile341 (accessed [today's date]).

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