Is ACTG1 p.Ser348= (c.1044A>T) pathogenic?

ACTG1 p.Ser348= (c.1044A>T) is classified Likely benign in ACTG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Very rare (popmax 0.00167%, amr); Associated with Baraitser-winter syndrome 2.

What condition is associated with ACTG1 p.Ser348= (c.1044A>T)?

ACTG1 p.Ser348= (c.1044A>T) is associated with Baraitser-winter syndrome 2, autosomal dominant nonsyndromic hearing loss 20 (ClinVar).

How common is ACTG1 p.Ser348= (c.1044A>T) in the general population?

ACTG1 p.Ser348= (c.1044A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

ACTG1 p.Ser348=

c.1044A>T · rs782271572 · VCV2053528

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 2

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 -11	GERP -3.8
Overall
CADD	4.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,684 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
European (non-Finnish)	0.000339%	294,995

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: ACTG1
Protein: p.Ser348=
Coding: c.1044A>T
MANE Select: NM_001614
dbSNP: rs782271572
Type: single nucleotide variant
Location: chr17:81510774 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 348: an α-helix

Full ACTG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Baraitser-winter syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 20

Similar variants

ACTG1 p.Ala135Val Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Ala204Gly Likely pathogenic ★★ same condition
ACTG1 p.Arg183Gln Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Arg183Trp Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Arg206Gln Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Arg210Cys Pathogenic ★★ same condition
ACTG1 p.Arg254Trp Pathogenic/Likely pathogenic ★★ same condition
ACTG1 p.Arg335His Pathogenic/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/actg1-p-ser348 (accessed [today's date]).

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