Is APOB p.Ala2365Asp (c.7094C>A) pathogenic?

APOB p.Ala2365Asp (c.7094C>A) is classified Uncertain significance in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-17). AlphaMissense: ambiguous (0.4498); Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ala2365Asp (c.7094C>A)?

APOB p.Ala2365Asp (c.7094C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOB p.Ala2365Asp (c.7094C>A) in the general population?

APOB p.Ala2365Asp (c.7094C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about APOB p.Ala2365Asp (c.7094C>A)?

AlphaMissense predicts ambiguous (score 0.4498) — an in-silico prediction, not a clinical call.

APOB p.Ala2365Asp

c.7094C>A · rs200034452 · VCV2586190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4498	ambiguous
REVEL	0.122	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.77, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,629 bp · p 0.051 · regional, not allelic
Overall
CADD	18.44	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 0.00133% African / African-American · 1/74,976 alleles

Overall 6.84e-05% 1/1,461,676 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: APOB
Protein: p.Ala2365Asp
Coding: c.7094C>A
MANE Select: NM_000384
dbSNP: rs200034452
Type: single nucleotide variant
Location: chr2:21009774 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2365: a UniProt-annotated variant site (in)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOB p.Ala2365= Likely benign ★★ same residue
APOB p.Ala2365Val Conflicting classifications of pathogenicity ★ ⚠ same residue
APOB p.Arg490Trp Pathogenic/Likely pathogenic ★★ same condition
APOB c.1124+3A>G Uncertain significance ★★ same condition
APOB c.11788+4A>G Uncertain significance ★★ same condition
APOB c.12087+2T>C Uncertain significance ★★ same condition
APOB p.Ala1320Thr Uncertain significance ★★ ⚠ same condition
APOB p.Ala1695Val 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/apob-p-ala2365asp (accessed [today's date]).

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