Is ACTG1 p.Ile369= (c.1107C>T) pathogenic?

ACTG1 p.Ile369= (c.1107C>T) is classified Likely benign in ACTG1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0641%, afr); Associated with Baraitser-winter syndrome 2.

What condition is associated with ACTG1 p.Ile369= (c.1107C>T)?

ACTG1 p.Ile369= (c.1107C>T) is associated with Baraitser-winter syndrome 2, autosomal dominant nonsyndromic hearing loss 20 (ClinVar).

How common is ACTG1 p.Ile369= (c.1107C>T) in the general population?

ACTG1 p.Ile369= (c.1107C>T) is ultra-rare (popmax 0.0641%, afr) (gnomAD).

ACTG1 p.Ile369=

c.1107C>T · rs372665803 · VCV772175

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0641%, afr)

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 -0.68	GERP -1.9
Overall
CADD	7.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0641% African / African-American · 48/74,916 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0445%

Overall 0.00967% 156/1,613,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0641%	1,561
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
Middle Eastern	0.0329%	3,035
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Admixed American	0.0117%	8,572
European (non-Finnish)	0.00602%	16,620
South Asian	0.00329%	30,361
East Asian	0.00223%	44,894

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.Ile369=
Coding: c.1107C>T
MANE Select: NM_001614
dbSNP: rs372665803
Type: single nucleotide variant
Location: chr17:81510711 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 95.44 · 11 PDB
Residue 369: an α-helix

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.Ile369Val 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-ile369 (accessed [today's date]).

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