Is BIN1 p.Ala512= (c.1536C>T) pathogenic?

BIN1 p.Ala512= (c.1536C>T) is classified Likely benign in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Very rare (popmax 0.00659%, sas); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Ala512= (c.1536C>T)?

BIN1 p.Ala512= (c.1536C>T) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Ala512= (c.1536C>T) in the general population?

BIN1 p.Ala512= (c.1536C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

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

BIN1 p.Ala512=

c.1536C>T · rs753612525 · VCV739363

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

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 -6.6	GERP -4
Overall
CADD	0.254	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,090 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00124% 20/1,613,656 alleles · very rare exomes 19/1,461,450 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,182
East Asian	0.00446%	22,446
African / African-American	0.00267%	37,467
Admixed American	0.00167%	60,006
European (non-Finnish)	0.000763%	131,114

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.Ala512=
Coding: c.1536C>T
MANE Select: NM_139343
dbSNP: rs753612525
Type: single nucleotide variant
Location: chr2:127050838 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.61 · 7 PDB

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.Ala512Thr 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-ala512 (accessed [today's date]).

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