Is BIN3 p.Thr151Met (c.452C>T) pathogenic?

BIN3 p.Thr151Met (c.452C>T) is classified Uncertain significance in BIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.4996); Very rare (popmax 0.00627%, nfe).

How common is BIN3 p.Thr151Met (c.452C>T) in the general population?

BIN3 p.Thr151Met (c.452C>T) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about BIN3 p.Thr151Met (c.452C>T)?

AlphaMissense predicts ambiguous (score 0.4996) — an in-silico prediction, not a clinical call.

BIN3 p.Thr151Met

c.452C>T · rs371543413 · VCV2459230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4996	ambiguous
REVEL	0.411	indeterminate
SaProt	LLR -12.93	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.041 · regional, not allelic
Overall
CADD	33.0	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 0.00627% European (non-Finnish) · 74/1,179,868 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00508% 82/1,613,752 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,944
Admixed American	0.005%	19,996
Remaining individualsnot grpmax-eligible	0.0032%	31,228
East Asian	0.00223%	44,888
South Asian	0.0022%	45,531

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: BIN3
Protein: p.Thr151Met
Coding: c.452C>T
MANE Select: NM_018688
dbSNP: rs371543413
Type: single nucleotide variant
Location: chr8:22624250 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.83
Residue 151: the bar domain

Full BIN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIN3 c.297+5C>T Benign ★★ same type
BIN3 p.Ala131Pro Uncertain significance ★ ⚠ same type
BIN3 p.Arg128Gln Uncertain significance ★ ⚠ same type
BIN3 p.Arg128Trp Uncertain significance ★ ⚠ same type
BIN3 p.Arg136Gly Uncertain significance ★ ⚠ same type
BIN3 p.Arg166Gln Uncertain significance ★ ⚠ same type
BIN3 p.Arg185Cys Uncertain significance ★ ⚠ same type
BIN3 p.Arg203Gln Uncertain significance ★ ⚠ same type

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/bin3-p-thr151met (accessed [today's date]).

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