Is ACTG1 p.Thr77= (c.231C>T) pathogenic?

ACTG1 p.Thr77= (c.231C>T) is classified Conflicting classifications of pathogenicity in ACTG1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-01). Rare (popmax 0.346%, mid); Associated with Baraitser-winter syndrome 2.

What condition is associated with ACTG1 p.Thr77= (c.231C>T)?

ACTG1 p.Thr77= (c.231C>T) is associated with Baraitser-winter syndrome 2, autosomal dominant nonsyndromic hearing loss 20 (ClinVar).

How common is ACTG1 p.Thr77= (c.231C>T) in the general population?

ACTG1 p.Thr77= (c.231C>T) is rare (popmax 0.346%, mid) (gnomAD).

ACTG1 p.Thr77=

c.231C>T · rs375450454 · VCV281581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.346%, mid)

Conditions

Baraitser-winter syndrome 2

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 4.5	GERP 1.9, phastCons 1
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.346% Middle Eastern · 21/6,062 alleles

Filtering AF 0.232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.0133% 215/1,614,060 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.346%	289
South Asian	0.105%	949
Admixed American	0.02%	5,003
Remaining individualsnot grpmax-eligible	0.0176%	5,683
European (non-Finnish)	0.0061%	16,389
African / African-American	0.00266%	37,529
East Asian	0.00223%	44,884

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.Thr77=
Coding: c.231C>T
MANE Select: NM_001614
dbSNP: rs375450454
Type: single nucleotide variant
Location: chr17:81512035 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 77: a β-strand

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

Disease context

Baraitser-winter syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 20

Similar variants

ACTG1 p.Thr77Ser Uncertain significance ★ ⚠ same residue
ACTG1 p.Thr77Ala 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-thr77 (accessed [today's date]).

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