Is ACTG1 p.Gly42= (c.126C>T) pathogenic?

ACTG1 p.Gly42= (c.126C>T) is classified Benign/Likely benign in ACTG1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-06-03). Ultra-rare (popmax 0.0621%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 20.

How common is ACTG1 p.Gly42= (c.126C>T) in the general population?

ACTG1 p.Gly42= (c.126C>T) is ultra-rare (popmax 0.0621%, nfe) (gnomAD).

ACTG1 p.Gly42=

Q: What condition is associated with ACTG1 p.Gly42= (c.126C>T)?

ACTG1 p.Gly42= (c.126C>T) is associated with autosomal dominant nonsyndromic hearing loss 20, Baraitser-winter syndrome 2 (ClinVar).

c.126C>T · rs11549197 · VCV379424

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0621%, nfe)

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 -0.97	GERP -3.7
Overall
CADD	10.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0621% European (non-Finnish) · 733/1,180,034 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0569%

Overall 0.0479% 773/1,613,532 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0621%	1,610
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,718
Finnishnot grpmax-eligible	0.00315%	31,709
East Asian	0.00223%	44,878

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.Gly42=
Coding: c.126C>T
MANE Select: NM_001614
dbSNP: rs11549197
Type: single nucleotide variant
Location: chr17:81512140 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB

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.Gly42Ser Uncertain significance ★ ⚠ same residue
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

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-gly42 (accessed [today's date]).

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