Is BIN1 p.Arg145fs (c.432del) pathogenic?

BIN1 p.Arg145fs (c.432del) is classified Likely pathogenic in BIN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.00133%, afr); Associated with BIN1-related disorder.

What condition is associated with BIN1 p.Arg145fs (c.432del)?

BIN1 p.Arg145fs (c.432del) is associated with BIN1-related disorder (ClinVar).

How common is BIN1 p.Arg145fs (c.432del) in the general population?

BIN1 p.Arg145fs (c.432del) is very rare (popmax 0.00133%, afr) (gnomAD).

BIN1 p.Arg145fs

c.432del · VCV3348477

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

BIN1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 2.1, phastCons 1
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Overall 6.2e-05% 1/1,613,958 alleles · very rare exomes 0/1,461,774 · genomes 1/152,184 · joint denominator

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: BIN1
Protein: p.Arg145fs
Coding: c.432del
MANE Select: NM_139343
Type: Deletion
Location: chr2:127069011 (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 145: the bar domain; a UniProt-annotated variant site (in cnm2); an α-helix

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

Disease context

BIN1-related disorder

Similar variants

BIN1 p.Arg145Cys Likely pathogenic ★★ same residue
BIN1 p.Arg145His Uncertain significance ★ ⚠ same residue
BIN1 p.Arg145Ser Uncertain significance ★ ⚠ same residue
BIN1 c.1132-22TGC[5] Likely benign same condition
BIN1 p.Tyr114= Likely benign same condition
BIN1 c.166-2_220+3del Likely pathogenic ★ same type
BIN1 c.1264-11_1270del Conflicting classifications of pathogenicity ★ same type
BIN1 c.*479del 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-arg145fs (accessed [today's date]).

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