Is APBB2 p.Leu382Ile (c.1144T>A) pathogenic?

APBB2 p.Leu382Ile (c.1144T>A) is classified Uncertain significance in APBB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely pathogenic (0.862); Absent from gnomAD v4.1.

How common is APBB2 p.Leu382Ile (c.1144T>A) in the general population?

APBB2 p.Leu382Ile (c.1144T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APBB2 p.Leu382Ile (c.1144T>A)?

AlphaMissense predicts likely pathogenic (score 0.862) — an in-silico prediction, not a clinical call.

APBB2 p.Leu382Ile

c.1144T>A · rs2550666688 · VCV2254956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.862	likely pathogenic
REVEL	0.141	moderately benign-leaning
SaProt	LLR -5.16	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 6.3	GERP 0.52, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 217 kb · p 1.3e-10 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L381I vs ClinVar L382I) — verify the residue.

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: APBB2
Protein: p.Leu382Ile
Coding: c.1144T>A
MANE Select: NM_004307
dbSNP: rs2550666688
Type: single nucleotide variant
Location: chr4:40934663 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.61 (gnomAD)
Structure: AlphaFold pLDDT 61.73

Full APBB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB2 c.20-6C>T Benign ★★ same type
APBB2 p.Ala111Val Uncertain significance ★ ⚠ same type
APBB2 p.Ala126Val Uncertain significance ★ ⚠ same type
APBB2 p.Ala197Val Uncertain significance ★ ⚠ same type
APBB2 p.Ala224Asp Uncertain significance ★ ⚠ same type
APBB2 p.Ala279Val Uncertain significance ★ same type
APBB2 p.Ala436Pro Uncertain significance ★ ⚠ same type
APBB2 p.Ala436Thr 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/apbb2-p-leu382ile (accessed [today's date]).

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