Is BIN1 p.Pro491fs (c.1470del) pathogenic?

BIN1 p.Pro491fs (c.1470del) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). Absent from gnomAD; Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Pro491fs (c.1470del)?

BIN1 p.Pro491fs (c.1470del) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Pro491fs (c.1470del) in the general population?

BIN1 p.Pro491fs (c.1470del) is absent from gnomAD (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

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

BIN1 p.Pro491fs

c.1470del · rs2467164775 · VCV2019038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

myopathy, centronuclear, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BIN1
Protein: p.Pro491fs
Coding: c.1470del
MANE Select: NM_139343
dbSNP: rs2467164775
Type: Deletion
Location: chr2:127050904 (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.Pro491= Conflicting classifications of pathogenicity ★ same residue
BIN1 c.166-2_220+3del Likely pathogenic ★ same condition
BIN1 c.1264-11_1270del Conflicting classifications of pathogenicity ★ same condition
BIN1 p.Ala122fs Uncertain significance ★ same condition
BIN1 p.Asp545fs Uncertain significance ★ same condition
BIN1 p.Glu379fs Uncertain significance ★ same condition
BIN1 p.Gly144del Uncertain significance ★ same condition
BIN1 p.Pro324_Thr327del 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-pro491fs (accessed [today's date]).

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