Is BIN1 p.Ala319= (c.957C>A) pathogenic?

BIN1 p.Ala319= (c.957C>A) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2013-03-04). Very rare (popmax 8.61e-05%, nfe); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Ala319= (c.957C>A)?

BIN1 p.Ala319= (c.957C>A) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Ala319= (c.957C>A) in the general population?

BIN1 p.Ala319= (c.957C>A) is very rare (popmax 8.61e-05%, nfe) (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

BIN1 p.Ala319=

c.957C>A · rs2276579 · VCV158023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.61e-05%, nfe)

Conditions

myopathy, centronuclear, 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 -0.12	GERP -2.6
Overall
CADD	1.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.61e-05% European (non-Finnish) · 1/1,161,174 alleles

Overall 6.34e-05% 1/1,576,264 alleles · very rare exomes 1/1,424,154 · genomes 0/152,110 · 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: BIN1
Protein: p.Ala319=
Coding: c.957C>A
MANE Select: NM_139343
dbSNP: rs2276579
Type: single nucleotide variant
Location: chr2:127059056 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.61 · 7 PDB
Residue 319: the 'disordered' region

Full BIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopathy, centronuclear, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive centronuclear myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

BIN1 p.Ala319Thr Uncertain significance ★ ⚠ same residue
BIN1 p.Arg145Cys Likely pathogenic ★★ same condition
BIN1 p.Arg234Cys Pathogenic/Likely pathogenic ★★ same condition
BIN1 c.165+6T>C Uncertain significance ★★ same condition
BIN1 c.-163T>C Uncertain significance ★★ same condition
BIN1 p.Ala104Ser Uncertain significance ★★ ⚠ same condition
BIN1 p.Ala289Thr Uncertain significance ★★ ⚠ same condition
BIN1 p.Ala289Val 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/bin1-p-ala319 (accessed [today's date]).

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