Is APOB p.Val4080= (c.12240C>G) pathogenic?

APOB p.Val4080= (c.12240C>G) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). Very rare (popmax 0.00134%, afr); Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Val4080= (c.12240C>G)?

APOB p.Val4080= (c.12240C>G) is associated with familial hypobetalipoproteinemia 1, hypercholesterolemia, autosomal dominant, type B (ClinVar).

How common is APOB p.Val4080= (c.12240C>G) in the general population?

APOB p.Val4080= (c.12240C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

APOB p.Val4080=

c.12240C>G · rs1337102534 · VCV765524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

familial hypobetalipoproteinemia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2.2, phastCons 1
Overall
CADD	1.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,880 alleles

Overall 6.2e-05% 1/1,613,808 alleles · very rare exomes 0/1,461,732 · genomes 1/152,076 · joint denominator

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.Val4080=
Coding: c.12240C>G
MANE Select: NM_000384
dbSNP: rs1337102534
Type: single nucleotide variant
Location: chr2:21003182 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Disease context

familial hypobetalipoproteinemia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypercholesterolemia, autosomal dominant, type B

Similar variants

APOB p.Val4080Phe Likely benign ★ same residue
APOB p.Val4080Ala 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

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-val4080 (accessed [today's date]).

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