Is BIN1 p.Ser303Phe (c.908C>T) pathogenic?

BIN1 p.Ser303Phe (c.908C>T) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-14). AlphaMissense: likely benign (0.1452); Very rare (popmax 0.000854%, nfe); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Ser303Phe (c.908C>T)?

BIN1 p.Ser303Phe (c.908C>T) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Ser303Phe (c.908C>T) in the general population?

BIN1 p.Ser303Phe (c.908C>T) is very rare (popmax 0.000854%, nfe) (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.Ser303Phe (c.908C>T)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

BIN1 p.Ser303Phe

c.908C>T · rs764752262 · VCV2439523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000854%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopathy, centronuclear, 2

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -10.69	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 58 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000854% European (non-Finnish) · 10/1,171,342 alleles

Filtering AF 0.000432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000315%

Overall 0.000693% 10/1,441,970 alleles · very rare

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.Ser303Phe
Coding: c.908C>T
MANE Select: NM_139343
dbSNP: rs764752262
Type: single nucleotide variant
Location: chr2:127059105 (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 303: a modified residue (phosphoserine); 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.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-ser303phe (accessed [today's date]).

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