Is BIN1 p.Ala481= (c.1443G>A) pathogenic?

BIN1 p.Ala481= (c.1443G>A) is classified Likely benign in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). Very rare (popmax 0.00288%, nfe); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Ala481= (c.1443G>A)?

BIN1 p.Ala481= (c.1443G>A) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Ala481= (c.1443G>A) in the general population?

BIN1 p.Ala481= (c.1443G>A) is very rare (popmax 0.00288%, 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.Ala481=

c.1443G>A · rs765816262 · VCV703348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00288%, 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 -3.3	GERP -3.5
Overall
CADD	11.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,179,936 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00236% 38/1,613,406 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,819
European (non-Finnish)grpmax	0.00288%	34,704
Admixed American	0.00167%	60,008

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala481=
Coding: c.1443G>A
MANE Select: NM_139343
dbSNP: rs765816262
Type: single nucleotide variant
Location: chr2:127051172 (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 481: 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.Ala481Val 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-ala481 (accessed [today's date]).

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