Is BIN1 p.Glu3Asp (c.9G>C) pathogenic?

BIN1 p.Glu3Asp (c.9G>C) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-16). AlphaMissense: likely benign (0.2085); Ultra-rare (popmax 0.0825%, sas); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Glu3Asp (c.9G>C)?

BIN1 p.Glu3Asp (c.9G>C) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Glu3Asp (c.9G>C) in the general population?

BIN1 p.Glu3Asp (c.9G>C) is ultra-rare (popmax 0.0825%, sas) (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

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

What do computational predictors say about BIN1 p.Glu3Asp (c.9G>C)?

AlphaMissense predicts likely benign (score 0.2085) — an in-silico prediction, not a clinical call.

BIN1 p.Glu3Asp

c.9G>C · rs558639756 · VCV461714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopathy, centronuclear, 2

Computational evidence

Protein change
AlphaMissense	0.2085	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP -0.74, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 58 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0825% South Asian · 75/90,888 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0619%

Overall 0.0049% 79/1,611,928 alleles · ultra-rare exomes 75/1,459,634 · genomes 4/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.00481%	20,806
European (non-Finnish)	8.48e-05%	1,179,377

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.Glu3Asp
Coding: c.9G>C
MANE Select: NM_139343
dbSNP: rs558639756
Type: single nucleotide variant
Location: chr2:127106935 (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 3: the 'interaction with bin2' 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.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
BIN1 p.Ala322Val 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-glu3asp (accessed [today's date]).

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