Is BIN3 p.Asp44Glu (c.132C>G) pathogenic?

BIN3 p.Asp44Glu (c.132C>G) is classified Uncertain significance in BIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely pathogenic (0.8516); Very rare (popmax 0.00137%, afr).

How common is BIN3 p.Asp44Glu (c.132C>G) in the general population?

BIN3 p.Asp44Glu (c.132C>G) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about BIN3 p.Asp44Glu (c.132C>G)?

AlphaMissense predicts likely pathogenic (score 0.8516) — an in-silico prediction, not a clinical call.

BIN3 p.Asp44Glu

c.132C>G · VCV3824354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8516	likely pathogenic
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.67, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.041 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00137% African / African-American · 1/73,110 alleles

Overall 0.000129% 2/1,552,822 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,110
South Asian	0.00119%	84,134

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: BIN3
Protein: p.Asp44Glu
Coding: c.132C>G
MANE Select: NM_018688
Type: single nucleotide variant
Location: chr8:22636553 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.83
Residue 44: the bar domain

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

Similar variants

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
BIN3 p.Arg185Cys Uncertain significance ★ ⚠ same type
BIN3 p.Arg203Gln 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-asp44glu (accessed [today's date]).

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