Is APBB3 p.Arg382Leu (c.1145G>T) pathogenic?

APBB3 p.Arg382Leu (c.1145G>T) is classified Uncertain significance in APBB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1107); Very rare (popmax 0.00666%, amr).

How common is APBB3 p.Arg382Leu (c.1145G>T) in the general population?

APBB3 p.Arg382Leu (c.1145G>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about APBB3 p.Arg382Leu (c.1145G>T)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

APBB3 p.Arg382Leu

c.1145G>T · rs553019305 · VCV3127702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -7.90	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 -1.2	GERP -4.3, phastCons 0.001
Regional constraint	o/e 0.33	constrained · MANE · 46 bp · p 0.0018 · regional, not allelic
Overall
CADD	16.63	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

Grpmax group 0.00666% Admixed American · 4/60,030 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,461,876 alleles · very rare

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: APBB3
Protein: p.Arg382Leu
Coding: c.1145G>T
MANE Select: NM_133173
dbSNP: rs553019305
Type: single nucleotide variant
Location: chr5:140560392 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.76 · 2 PDB
Residue 382: a β-strand; the pid 2 domain

Full APBB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB3 p.Arg382His Uncertain significance ★ ⚠ same residue
APBB3 p.Ala135Gly Uncertain significance ★ ⚠ same type
APBB3 p.Ala151Val Uncertain significance ★ ⚠ same type
APBB3 p.Ala163Thr Uncertain significance ★ ⚠ same type
APBB3 p.Ala288Thr Uncertain significance ★ ⚠ same type
APBB3 p.Ala313Val Uncertain significance ★ ⚠ same type
APBB3 p.Ala475Asp Uncertain significance ★ same type
APBB3 p.Arg122Cys 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/apbb3-p-arg382leu (accessed [today's date]).

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