Is ACTB p.Lys373= (c.1119A>G) pathogenic?

ACTB p.Lys373= (c.1119A>G) is classified Likely benign in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). Very rare (popmax 0.00167%, amr); Associated with Baraitser-Winter syndrome 1.

What condition is associated with ACTB p.Lys373= (c.1119A>G)?

ACTB p.Lys373= (c.1119A>G) is associated with Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Lys373= (c.1119A>G) in the general population?

ACTB p.Lys373= (c.1119A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

ACTB p.Lys373=

c.1119A>G · VCV3725801

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, 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 -1.5	GERP -2.2
Overall
CADD	7.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,976 alleles

Overall 0.000124% 2/1,613,610 alleles · very rare exomes 1/1,461,568 · genomes 1/152,042 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
Finnishnot grpmax-eligible	0.00156%	63,998

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.Lys373=
Coding: c.1119A>G
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5527757 (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.Lys373Ter 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
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-lys373 (accessed [today's date]).

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