Is ACTG1 p.Ile5= (c.15C>T) pathogenic?

ACTG1 p.Ile5= (c.15C>T) is classified Benign/Likely benign in ACTG1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.06%, sas); Associated with Baraitser-winter syndrome 2.

What condition is associated with ACTG1 p.Ile5= (c.15C>T)?

ACTG1 p.Ile5= (c.15C>T) is associated with Baraitser-winter syndrome 2, autosomal dominant nonsyndromic hearing loss 20 (ClinVar).

How common is ACTG1 p.Ile5= (c.15C>T) in the general population?

ACTG1 p.Ile5= (c.15C>T) is low-frequency (popmax 1.06%, sas) (gnomAD).

ACTG1 p.Ile5=

c.15C>T · rs199657153 · VCV210092

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, sas)

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 -0.043	GERP -3.6, phastCons 0.24
Overall
CADD	5.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.06% South Asian · 965/91,078 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.982%

Overall 0.0674% 1,088/1,613,958 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.06%	94
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Admixed American	0.0167%	6,003
Middle Eastern	0.0165%	6,062
African / African-American	0.008%	12,504
European (non-Finnish)	0.00542%	18,437
East Asian	0.00223%	44,870

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.Ile5=
Coding: c.15C>T
MANE Select: NM_001614
dbSNP: rs199657153
Type: single nucleotide variant
Location: chr17:81512340 (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

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.Ile5Val 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-ile5 (accessed [today's date]).

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