Is BIN2 p.Ala121Val (c.362C>T) pathogenic?

BIN2 p.Ala121Val (c.362C>T) is classified Uncertain significance in BIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.1158); Absent from gnomAD v4.1.

How common is BIN2 p.Ala121Val (c.362C>T) in the general population?

BIN2 p.Ala121Val (c.362C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIN2 p.Ala121Val (c.362C>T)?

AlphaMissense predicts likely benign (score 0.1158) — an in-silico prediction, not a clinical call.

BIN2 p.Ala121Val

c.362C>T · VCV3480678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1158 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1158	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP -0.54, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 43 kb · p 0.00047 · regional, not allelic
Overall
CADD	20.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BIN2
Protein: p.Ala121Val
Coding: c.362C>T
MANE Select: NM_016293
Type: single nucleotide variant
Location: chr12:51302066 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.40 · 2 PDB
Residue 121: the bar domain; an α-helix

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

Similar variants

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
BIN2 p.Arg202Cys 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-ala121val (accessed [today's date]).

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