Is STAC3 p.Phe97Val (c.289T>G) pathogenic?

STAC3 p.Phe97Val (c.289T>G) is classified Uncertain significance in STAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). AlphaMissense: likely pathogenic (0.8695); Very rare (popmax 8.49e-05%, nfe); Associated with Bailey-Bloch congenital myopathy.

What condition is associated with STAC3 p.Phe97Val (c.289T>G)?

STAC3 p.Phe97Val (c.289T>G) is associated with Bailey-Bloch congenital myopathy (ClinVar).

How common is STAC3 p.Phe97Val (c.289T>G) in the general population?

STAC3 p.Phe97Val (c.289T>G) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about STAC3 p.Phe97Val (c.289T>G)?

AlphaMissense predicts likely pathogenic (score 0.8695) — an in-silico prediction, not a clinical call.

STAC3 p.Phe97Val

c.289T>G · VCV4691038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bailey-Bloch congenital myopathy

Computational evidence

Protein change
AlphaMissense	0.8695	likely pathogenic
REVEL	0.77	pathogenic-leaning
SaProt	LLR -11.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,821 bp · p 0.043 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,908 alleles

Overall 6.21e-05% 1/1,610,224 alleles · very rare exomes 1/1,457,910 · genomes 0/152,314 · joint denominator

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: STAC3
Protein: p.Phe97Val
Coding: c.289T>G
MANE Select: NM_145064
Type: single nucleotide variant
Location: chr12:57249086 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 5 PDB

Full STAC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bailey-Bloch congenital myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAC3 p.Lys288Ter Pathogenic/Likely pathogenic ★★ same condition
STAC3 p.Trp284Ser Pathogenic/Likely pathogenic ★★ same condition
STAC3 p.Ala341Val Uncertain significance ★★ ⚠ same condition
STAC3 p.Arg108Gln Uncertain significance ★★ same condition
STAC3 p.Arg173Cys Uncertain significance ★★ ⚠ same condition
STAC3 p.Arg182His Uncertain significance ★★ same condition
STAC3 p.Arg321His Uncertain significance ★★ ⚠ same condition
STAC3 p.Arg351Leu Uncertain significance ★★ ⚠ 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/stac3-p-phe97val (accessed [today's date]).

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