Is BIN2 p.Gly95Ser (c.283G>A) pathogenic?

BIN2 p.Gly95Ser (c.283G>A) is classified Uncertain significance in BIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: ambiguous (0.5417); Ultra-rare (popmax 0.01%, amr).

How common is BIN2 p.Gly95Ser (c.283G>A) in the general population?

BIN2 p.Gly95Ser (c.283G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about BIN2 p.Gly95Ser (c.283G>A)?

AlphaMissense predicts ambiguous (score 0.5417) — an in-silico prediction, not a clinical call.

BIN2 p.Gly95Ser

c.283G>A · VCV4209064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5417 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Computational evidence

Protein change
AlphaMissense	0.5417	ambiguous
REVEL	0.397	indeterminate
SaProt	LLR -12.78	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00047 · regional, not allelic
Overall
CADD	24.0	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 0.01% Admixed American · 6/59,988 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00167% 27/1,613,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0064%	15,621
African / African-American	0.00133%	74,914
European (non-Finnish)	0.00127%	78,664
South Asian	0.0011%	91,076

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: BIN2
Protein: p.Gly95Ser
Coding: c.283G>A
MANE Select: NM_016293
Type: single nucleotide variant
Location: chr12:51302715 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.40 · 2 PDB
Residue 95: the bar domain

Full BIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIN2 p.Gly95Asp Uncertain significance ★ ⚠ same residue
BIN2 p.Ala121Val Uncertain significance ★ ⚠ same type
BIN2 p.Ala130Thr Uncertain significance ★ ⚠ same type
BIN2 p.Ala158Thr Uncertain significance ★ ⚠ same type
BIN2 p.Ala344Val Uncertain significance ★ ⚠ same type
BIN2 p.Ala384Thr Uncertain significance ★ ⚠ same type
BIN2 p.Arg123Lys Uncertain significance ★ ⚠ same type
BIN2 p.Arg138Thr 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/bin2-p-gly95ser (accessed [today's date]).

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