Is ACTG1 p.Gly343= (c.1029C>T) pathogenic?

ACTG1 p.Gly343= (c.1029C>T) is classified Benign/Likely benign in ACTG1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.197%, sas); Associated with autosomal dominant nonsyndromic hearing loss 20.

What condition is associated with ACTG1 p.Gly343= (c.1029C>T)?

ACTG1 p.Gly343= (c.1029C>T) is associated with autosomal dominant nonsyndromic hearing loss 20, Baraitser-winter syndrome 2 (ClinVar).

How common is ACTG1 p.Gly343= (c.1029C>T) in the general population?

ACTG1 p.Gly343= (c.1029C>T) is rare (popmax 0.197%, sas) (gnomAD).

ACTG1 p.Gly343=

c.1029C>T · rs143659814 · VCV516556

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, sas)

Conditions

autosomal dominant nonsyndromic hearing loss 20

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 4.4	GERP 0.76, phastCons 1
Overall
CADD	7.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% South Asian · 179/91,012 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.166%

Overall 0.159% 2,565/1,612,124 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.277%	361
South Asiangrpmax	0.197%	508
European (non-Finnish)	0.175%	572
East Asian	0.154%	648
Remaining individualsnot grpmax-eligible	0.149%	672
Admixed American	0.0885%	1,130
Middle Eastern	0.033%	3,030
African / African-American	0.0323%	3,100
Finnishnot grpmax-eligible	0.00157%	63,792

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly343=
Coding: c.1029C>T
MANE Select: NM_001614
dbSNP: rs143659814
Type: single nucleotide variant
Location: chr17:81510789 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 343: an α-helix

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

Disease context

autosomal dominant nonsyndromic hearing loss 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baraitser-winter syndrome 2

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-gly343 (accessed [today's date]).

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