Is BIN1 p.Arg202Ter (c.604C>T) pathogenic?

BIN1 p.Arg202Ter (c.604C>T) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-21). Ultra-rare (popmax 0.0165%, mid); Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Arg202Ter (c.604C>T)?

BIN1 p.Arg202Ter (c.604C>T) is associated with myopathy, centronuclear, 2 (ClinVar).

How common is BIN1 p.Arg202Ter (c.604C>T) in the general population?

BIN1 p.Arg202Ter (c.604C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Autosomal recessive centronuclear myopathy inherited?

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

BIN1 p.Arg202Ter

c.604C>T · rs762897872 · VCV1010127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

myopathy, centronuclear, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 19
Splicing
SpliceAI	Δ0.28	donor loss, 8 bp away · masked 0 · deltas
Pangolin	Δ0.36	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	49.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,266 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00167%	59,980
European (non-Finnish)	0.000254%	393,272

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.Arg202Ter
Coding: c.604C>T
MANE Select: NM_139343
dbSNP: rs762897872
Type: single nucleotide variant
Location: chr2:127068171 (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 202: the bar domain

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-arg202ter (accessed [today's date]).

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