Is BIN2 p.Gly4Ser (c.10G>A) pathogenic?

BIN2 p.Gly4Ser (c.10G>A) is classified Uncertain significance in BIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). AlphaMissense: likely benign (0.1512); Ultra-rare (popmax 0.01%, amr).

How common is BIN2 p.Gly4Ser (c.10G>A) in the general population?

BIN2 p.Gly4Ser (c.10G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about BIN2 p.Gly4Ser (c.10G>A)?

AlphaMissense predicts likely benign (score 0.1512) — an in-silico prediction, not a clinical call.

BIN2 p.Gly4Ser

c.10G>A · VCV3480672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1512 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1512	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.53, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00047 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 · 6/59,978 alleles

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

Overall 0.00093% 15/1,613,302 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,996
European (non-Finnish)	0.000763%	131,074

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.Gly4Ser
Coding: c.10G>A
MANE Select: NM_016293
Type: single nucleotide variant
Location: chr12:51324093 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.40 · 2 PDB

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

Similar variants

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
BIN2 p.Arg142Trp 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-gly4ser (accessed [today's date]).

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