Is ACTG1 p.Ala230= (c.690C>T) pathogenic?

ACTG1 p.Ala230= (c.690C>T) is classified Likely benign in ACTG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-18). Ultra-rare (popmax 0.0367%, amr); Associated with autosomal dominant nonsyndromic hearing loss 20.

What condition is associated with ACTG1 p.Ala230= (c.690C>T)?

ACTG1 p.Ala230= (c.690C>T) is associated with autosomal dominant nonsyndromic hearing loss 20, Baraitser-winter syndrome 2 (ClinVar).

How common is ACTG1 p.Ala230= (c.690C>T) in the general population?

ACTG1 p.Ala230= (c.690C>T) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

ACTG1 p.Ala230=

c.690C>T · rs11549213 · VCV379382

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

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 -12	GERP -3.8
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/60,020 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00923% 149/1,613,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0128%	7,813
African / African-American	0.012%	8,340
European (non-Finnish)	0.00881%	11,347
East Asian	0.00446%	22,442
South Asian	0.00439%	22,772

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.Ala230=
Coding: c.690C>T
MANE Select: NM_001614
dbSNP: rs11549213
Type: single nucleotide variant
Location: chr17:81511300 (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.Ala230Asp Uncertain significance ★ ⚠ same residue
ACTG1 p.Ala230Thr Uncertain significance ★ ⚠ same residue
ACTG1 p.Ala230Val Likely pathogenic ★ 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

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-ala230 (accessed [today's date]).

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