Is BIN1 p.Ala205Val (c.614C>T) pathogenic?

BIN1 p.Ala205Val (c.614C>T) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-18). AlphaMissense: likely pathogenic (0.9639); Absent from gnomAD v4.1.

How common is BIN1 p.Ala205Val (c.614C>T) in the general population?

BIN1 p.Ala205Val (c.614C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIN1 p.Ala205Val (c.614C>T)?

AlphaMissense predicts likely pathogenic (score 0.9639) — an in-silico prediction, not a clinical call.

BIN1 p.Ala205Val

c.614C>T · rs2467339177 · VCV2136067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9639 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9639	likely pathogenic
REVEL	0.486	indeterminate
SaProt	LLR -12.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 58 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: BIN1
Protein: p.Ala205Val
Coding: c.614C>T
MANE Select: NM_139343
dbSNP: rs2467339177
Type: single nucleotide variant
Location: chr2:127064017 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.61 · 7 PDB
Residue 205: the bar domain; an α-helix

Full BIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BIN1 p.Ala205= Likely benign ★ same residue
BIN1 p.Arg145Cys Likely pathogenic ★★ same type
BIN1 p.Arg234Cys Pathogenic/Likely pathogenic ★★ same type
BIN1 c.165+6T>C Uncertain significance ★★ same type
BIN1 c.-163T>C Uncertain significance ★★ same type
BIN1 p.Ala104Ser Uncertain significance ★★ ⚠ same type
BIN1 p.Ala289Thr Uncertain significance ★★ ⚠ same type
BIN1 p.Ala289Val 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/bin1-p-ala205val (accessed [today's date]).

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