Is BIN1 p.Ser487= (c.1461C>T) pathogenic?

BIN1 p.Ser487= (c.1461C>T) is classified Uncertain significance in BIN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0513%, eas); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Ser487= (c.1461C>T)?

BIN1 p.Ser487= (c.1461C>T) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Ser487= (c.1461C>T) in the general population?

BIN1 p.Ser487= (c.1461C>T) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

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

BIN1 p.Ser487=

c.1461C>T · rs34647988 · VCV158009

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

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 -0.3	GERP -1.4, phastCons 0.004
Overall
CADD	11.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0513% East Asian · 23/44,874 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0031% 50/1,613,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0513%	1,951
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.00833%	12,006
South Asian	0.00659%	15,179
African / African-American	0.00533%	18,763
European (non-Finnish)	0.000254%	393,301

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.Ser487=
Coding: c.1461C>T
MANE Select: NM_139343
dbSNP: rs34647988
Type: single nucleotide variant
Location: chr2:127051154 (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 487: 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.Ser487Cys 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-ser487 (accessed [today's date]).

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