Is BIN1 p.Pro381Ser (c.1141C>T) pathogenic?

BIN1 p.Pro381Ser (c.1141C>T) is classified Uncertain significance in BIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-24). AlphaMissense: likely benign (0.1077); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BIN1 p.Pro381Ser (c.1141C>T)?

BIN1 p.Pro381Ser (c.1141C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BIN1 p.Pro381Ser (c.1141C>T) in the general population?

BIN1 p.Pro381Ser (c.1141C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BIN1 p.Pro381Ser (c.1141C>T)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

BIN1 p.Pro381Ser

c.1141C>T · VCV3260934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -6.57	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 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 58 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	24.9	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: BIN1
Protein: p.Pro381Ser
Coding: c.1141C>T
MANE Select: NM_139343
Type: single nucleotide variant
Location: chr2:127054003 (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 381: the 'clathrin-binding' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BIN1 p.Pro381Leu Uncertain significance ★★ ⚠ same residue
BIN1 p.Pro381= Conflicting classifications of pathogenicity ★ same residue
BIN1 p.Ala380Thr Uncertain significance ★★ ⚠ same condition
BIN1 p.Ala465Val Uncertain significance ★★ ⚠ same condition
BIN1 p.Arg514His Uncertain significance ★★ ⚠ same condition
BIN1 p.Arg66Trp Uncertain significance ★★ ⚠ same condition
BIN1 p.Asp394Gly Uncertain significance ★★ ⚠ same condition
BIN1 p.Asp530Asn Uncertain significance ★★ same condition

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-pro381ser (accessed [today's date]).

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