Is ACTG1 p.Gln59= (c.177G>A) pathogenic?

ACTG1 p.Gln59= (c.177G>A) is classified Benign in ACTG1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-03). Common (popmax 5.73%, sas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 20.

ACTG1 p.Gln59=

Q: What condition is associated with ACTG1 p.Gln59= (c.177G>A)?

ACTG1 p.Gln59= (c.177G>A) is associated with autosomal dominant nonsyndromic hearing loss 20, Baraitser-winter syndrome 2 (ClinVar).

Q: How common is ACTG1 p.Gln59= (c.177G>A) in the general population?

ACTG1 p.Gln59= (c.177G>A) is common (popmax 5.73%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.177G>A · rs11549220 · VCV44146

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 5.73%, sas) — too common for a highly-penetrant pathogenic allele

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 3.9	GERP 0.7, phastCons 1
Overall
CADD	13.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% South Asian · 5,221/91,080 alleles

Filtering AF 5.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.55%

Overall 1.85% 29,879/1,613,906 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	5.73%	17
East Asian	5.02%	20
Admixed American	3.05%	33
Remaining individualsnot grpmax-eligible	1.79%	56
Finnishnot grpmax-eligible	1.56%	64
European (non-Finnish)	1.52%	66
Middle Eastern	1.44%	70
Ashkenazi Jewishnot grpmax-eligible	0.703%	142
Amishnot grpmax-eligible	0.329%	304
African / African-American	0.297%	337

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.Gln59=
Coding: c.177G>A
MANE Select: NM_001614
dbSNP: rs11549220
Type: single nucleotide variant
Location: chr17:81512089 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 59: 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.Gln59Arg Uncertain significance ★ ⚠ same residue
ACTG1 p.Gln59His 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

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-gln59 (accessed [today's date]).

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