Is APOB p.Asp148Asn (c.442G>A) pathogenic?

APOB p.Asp148Asn (c.442G>A) is classified Uncertain significance in APOB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-09). AlphaMissense: likely benign (0.0735); Very rare (popmax 0.000169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Asp148Asn (c.442G>A)?

APOB p.Asp148Asn (c.442G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is APOB p.Asp148Asn (c.442G>A) in the general population?

APOB p.Asp148Asn (c.442G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about APOB p.Asp148Asn (c.442G>A)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

APOB p.Asp148Asn

c.442G>A · rs757289663 · VCV2618326

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.216	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.86, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	16.52	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 0.000169% European (non-Finnish) · 2/1,180,048 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,092 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.Asp148Asn
Coding: c.442G>A
MANE Select: NM_000384
dbSNP: rs757289663
Type: single nucleotide variant
Location: chr2:21038053 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 148: 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

Similar variants

APOB p.Asp148= Likely benign ★★ 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
APOB p.Ala1975Ser 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-asp148asn (accessed [today's date]).

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