Is BIN1 p.Tyr238= (c.714C>T) pathogenic?

BIN1 p.Tyr238= (c.714C>T) is classified Benign in BIN1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele; Associated with myopathy, centronuclear, 2.

What condition is associated with BIN1 p.Tyr238= (c.714C>T)?

BIN1 p.Tyr238= (c.714C>T) is associated with myopathy, centronuclear, 2 (ClinVar).

How is Autosomal recessive centronuclear myopathy inherited?

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

BIN1 p.Tyr238=

Q: How common is BIN1 p.Tyr238= (c.714C>T) in the general population?

BIN1 p.Tyr238= (c.714C>T) is common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.714C>T · rs1137845 · VCV158018

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 17.3%, amr) — too common for a highly-penetrant pathogenic allele

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 -7.8	GERP -4.1
Overall
CADD	0.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.3% Admixed American · 10,319/59,818 alleles

Filtering AF 17% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.9%

Overall 4.53% 73,132/1,613,502 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	17.3%	6
South Asian	14.5%	7
East Asian	14%	7
Finnishnot grpmax-eligible	8.58%	12
Ashkenazi Jewishnot grpmax-eligible	5.21%	19
Middle Eastern	4.78%	21
Remaining individualsnot grpmax-eligible	4.75%	21
European (non-Finnish)	2.69%	37
African / African-American	1.83%	55
Amishnot grpmax-eligible	0.987%	101

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.Tyr238=
Coding: c.714C>T
MANE Select: NM_139343
dbSNP: rs1137845
Type: single nucleotide variant
Location: chr2:127063631 (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 238: the bar domain; an α-helix

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-tyr238 (accessed [today's date]).

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