Is BIN3 p.Ser229Tyr (c.686C>A) pathogenic?

BIN3 p.Ser229Tyr (c.686C>A) is classified Uncertain significance in BIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.264); Absent from gnomAD v4.1.

How common is BIN3 p.Ser229Tyr (c.686C>A) in the general population?

BIN3 p.Ser229Tyr (c.686C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIN3 p.Ser229Tyr (c.686C>A)?

AlphaMissense predicts likely benign (score 0.264) — an in-silico prediction, not a clinical call.

BIN3 p.Ser229Tyr

c.686C>A · rs2117487246 · VCV2271759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.264 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.264	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -14.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.21, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.041 · regional, not allelic
Overall
CADD	21.8	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

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: BIN3
Protein: p.Ser229Tyr
Coding: c.686C>A
MANE Select: NM_018688
dbSNP: rs2117487246
Type: single nucleotide variant
Location: chr8:22621498 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.83
Residue 229: the bar domain; the 'disordered' region

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

Similar variants

BIN3 p.Ser229Phe Uncertain significance ★ ⚠ same residue
BIN3 p.Ser229= Likely benign ★ same residue
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

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-ser229tyr (accessed [today's date]).

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