Is APOB p.Ala433Val (c.1298C>T) pathogenic?

APOB p.Ala433Val (c.1298C>T) is classified Likely benign in APOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). AlphaMissense: likely benign (0.2911); Rare (popmax 0.136%, eas); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ala433Val (c.1298C>T)?

APOB p.Ala433Val (c.1298C>T) is associated with Cardiovascular phenotype, hypercholesterolemia, autosomal dominant, type B, familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Ala433Val (c.1298C>T) in the general population?

APOB p.Ala433Val (c.1298C>T) is rare (popmax 0.136%, eas) (gnomAD).

What do computational predictors say about APOB p.Ala433Val (c.1298C>T)?

AlphaMissense predicts likely benign (score 0.2911) — an in-silico prediction, not a clinical call.

APOB p.Ala433Val

c.1298C>T · rs13306190 · VCV199683

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2911 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2911	likely benign
REVEL	0.437	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	24.8	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 0.136% East Asian · 61/44,874 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0987%

Overall 0.00793% 128/1,614,004 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.136%	736
European (non-Finnish)	0.00492%	20,345
Remaining individualsnot grpmax-eligible	0.0048%	20,836
South Asian	0.00439%	22,772
Finnishnot grpmax-eligible	0.00313%	31,928

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.Ala433Val
Coding: c.1298C>T
MANE Select: NM_000384
dbSNP: rs13306190
Type: single nucleotide variant
Location: chr2:21032408 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 433: the vitellogenin domain

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

Also linked: hypercholesterolemia, autosomal dominant, type B familial hypobetalipoproteinemia 1

Similar variants

APOB p.Ala433= Likely benign ★★ same residue
APOB c.1830-1G>A Pathogenic ★★ same condition
APOB c.2604+1G>A Likely pathogenic ★★ same condition
APOB c.537+1G>T Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg1333Ter Pathogenic ★★ same condition
APOB p.Arg2012Ter Pathogenic ★★ same condition
APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
APOB p.Arg2513Ter Pathogenic ★★ 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-ala433val (accessed [today's date]).

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