Is APOB p.Ser4338Asn (c.13013G>A) pathogenic?

APOB p.Ser4338Asn (c.13013G>A) is classified Benign in APOB (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0739); Common (popmax 85.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ser4338Asn (c.13013G>A)?

APOB p.Ser4338Asn (c.13013G>A) is associated with Cardiovascular phenotype, familial hypercholesterolemia, coumarin resistance (ClinVar).

What do computational predictors say about APOB p.Ser4338Asn (c.13013G>A)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

APOB p.Ser4338Asn

Q: How common is APOB p.Ser4338Asn (c.13013G>A) in the general population?

APOB p.Ser4338Asn (c.13013G>A) is common (popmax 85.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.13013G>A · rs1042034 · VCV128418

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 85.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.055	moderately 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 -0.1	GERP -3.2
Regional constraint	o/e 1.03	unconstrained · MANE · 9,629 bp · p 0.051 · regional, not allelic
Overall
CADD	0.127	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 85.2% African / African-American · 63,269/74,236 alleles

Filtering AF 84.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 84.4%

Overall 75.7% 1,209,586/1,598,072 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	85.2%	1
Ashkenazi Jewishnot grpmax-eligible	80.7%	1
European (non-Finnish)	79.1%	1
Amishnot grpmax-eligible	77.6%	1
Admixed American	75.1%	1
Remaining individualsnot grpmax-eligible	73.9%	1
Finnishnot grpmax-eligible	73.5%	1
Middle Eastern	68.1%	1
South Asian	49.2%	2
East Asian	26.6%	4

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.Ser4338Asn
Coding: c.13013G>A
MANE Select: NM_000384
dbSNP: rs1042034
Type: single nucleotide variant
Location: chr2:21002409 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 4338: 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

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

Similar variants

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
APOB p.Arg2520Ter Pathogenic/Likely 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-ser4338asn (accessed [today's date]).

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