Is STAC3 p.Pro43= (c.129C>G) pathogenic?

STAC3 p.Pro43= (c.129C>G) is classified Likely benign in STAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-06). Very rare (popmax 0.00254%, nfe); Associated with Bailey-Bloch congenital myopathy.

What condition is associated with STAC3 p.Pro43= (c.129C>G)?

STAC3 p.Pro43= (c.129C>G) is associated with Bailey-Bloch congenital myopathy (ClinVar).

How common is STAC3 p.Pro43= (c.129C>G) in the general population?

STAC3 p.Pro43= (c.129C>G) is very rare (popmax 0.00254%, nfe) (gnomAD).

STAC3 p.Pro43=

c.129C>G · rs1398254145 · VCV705086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Conditions

Bailey-Bloch congenital myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP 1.3, phastCons 1
Overall
CADD	9.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,179,936 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00192% 31/1,613,802 alleles · very rare exomes 29/1,461,658 · genomes 2/152,144 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,331
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Pro43=
Coding: c.129C>G
MANE Select: NM_145064
dbSNP: rs1398254145
Type: single nucleotide variant
Location: chr12:57249246 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.06 · 5 PDB
Residue 43: the 'disordered' region

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.Pro43Ser Uncertain significance ★ ⚠ same residue
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

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-pro43 (accessed [today's date]).

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