Is ACTB p.Ser348Leu (c.1043C>T) pathogenic?

ACTB p.Ser348Leu (c.1043C>T) is classified Pathogenic/Likely pathogenic in ACTB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-06-19). AlphaMissense: likely pathogenic (0.9977); Absent from gnomAD v4.1; Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Ser348Leu (c.1043C>T)?

ACTB p.Ser348Leu (c.1043C>T) is associated with Baraitser-Winter syndrome 1, intellectual disability (ClinVar).

How common is ACTB p.Ser348Leu (c.1043C>T) in the general population?

ACTB p.Ser348Leu (c.1043C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Ser348Leu (c.1043C>T)?

AlphaMissense predicts likely pathogenic (score 0.9977) — an in-silico prediction, not a clinical call.

ACTB p.Ser348Leu

c.1043C>T · rs886041309 · VCV279997

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.9977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Baraitser-Winter syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9977	likely pathogenic ✓ concordant with ClinVar
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -14.54	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 3.9	GERP 0.77, phastCons 1
Regional constraint	o/e 0.06	constrained · MANE · 132 bp · p 1.9e-13 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTB
Protein: p.Ser348Leu
Coding: c.1043C>T
MANE Select: NM_001101
dbSNP: rs886041309
Type: single nucleotide variant
Location: chr7:5527833 (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

Also linked: intellectual disability

Similar variants

ACTB p.Ser348= Benign/Likely benign ★★ 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
ACTB p.Arg196Leu Likely 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-ser348leu (accessed [today's date]).

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