Is ACTG1 p.Pro27= (c.81C>T) pathogenic?

ACTG1 p.Pro27= (c.81C>T) is classified Benign/Likely benign in ACTG1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-24). Rare (popmax 0.197%, sas); Associated with autosomal dominant nonsyndromic hearing loss 20.

How common is ACTG1 p.Pro27= (c.81C>T) in the general population?

ACTG1 p.Pro27= (c.81C>T) is rare (popmax 0.197%, sas) (gnomAD).

ACTG1 p.Pro27=

Q: What condition is associated with ACTG1 p.Pro27= (c.81C>T)?

ACTG1 p.Pro27= (c.81C>T) is associated with autosomal dominant nonsyndromic hearing loss 20, Baraitser-winter syndrome 2 (ClinVar).

c.81C>T · rs11549230 · VCV210095

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, sas)

Conditions

autosomal dominant nonsyndromic hearing loss 20

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.35	GERP -3.3, phastCons 0.97
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% South Asian · 179/91,082 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.0151% 244/1,613,804 alleles · rare exomes 231/1,461,532 · genomes 13/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.197%	509
Remaining individualsnot grpmax-eligible	0.016%	6,249
European (non-Finnish)	0.00441%	22,691
Admixed American	0.00333%	30,011
African / African-American	0.00133%	75,038

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.Pro27=
Coding: c.81C>T
MANE Select: NM_001614
dbSNP: rs11549230
Type: single nucleotide variant
Location: chr17:81512274 (GRCh38)

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

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-pro27 (accessed [today's date]).

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