Is APOB p.Ala618Val (c.1853C>T) pathogenic?

APOB p.Ala618Val (c.1853C>T) is classified Benign/Likely benign in APOB (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1362); Common (popmax 86.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Ala618Val (c.1853C>T)?

APOB p.Ala618Val (c.1853C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, coumarin resistance (ClinVar).

What do computational predictors say about APOB p.Ala618Val (c.1853C>T)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

APOB p.Ala618Val

Q: How common is APOB p.Ala618Val (c.1853C>T) in the general population?

APOB p.Ala618Val (c.1853C>T) is common (popmax 86.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1853C>T · rs679899 · VCV128420

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 86.2%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.429	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	26.7	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 86.2% East Asian · 38,655/44,836 alleles

Filtering AF 85.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.2%

Overall 47% 755,304/1,608,604 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	86.2%	1
South Asian	61%	2
Finnishnot grpmax-eligible	56%	2
Remaining individualsnot grpmax-eligible	46.9%	2
European (non-Finnish)	46.5%	2
Middle Eastern	45.3%	2
Admixed American	38.7%	3
Ashkenazi Jewishnot grpmax-eligible	37%	3
Amishnot grpmax-eligible	35.8%	3
African / African-American	16.7%	6

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.Ala618Val
Coding: c.1853C>T
MANE Select: NM_000384
dbSNP: rs679899
Type: single nucleotide variant
Location: chr2:21028042 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 618: the vitellogenin domain; 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-ala618val (accessed [today's date]).

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