Is APOB p.Val352Phe (c.1054G>T) pathogenic?

APOB p.Val352Phe (c.1054G>T) is classified Likely pathogenic in APOB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-12-01). AlphaMissense: likely pathogenic (0.5857); Very rare (popmax 8.47e-05%, nfe); Associated with familial hypobetalipoproteinemia 1.

What condition is associated with APOB p.Val352Phe (c.1054G>T)?

APOB p.Val352Phe (c.1054G>T) is associated with familial hypobetalipoproteinemia 1 (ClinVar).

How common is APOB p.Val352Phe (c.1054G>T) in the general population?

APOB p.Val352Phe (c.1054G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about APOB p.Val352Phe (c.1054G>T)?

AlphaMissense predicts likely pathogenic (score 0.5857) — an in-silico prediction, not a clinical call.

APOB p.Val352Phe

c.1054G>T · rs1572799173 · VCV827639

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

familial hypobetalipoproteinemia 1

Computational evidence

Protein change
AlphaMissense	0.5857	likely pathogenic ✓ concordant with ClinVar · top 8% in APOB
REVEL	0.503	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 32 kb · p 0.91 · regional, not allelic
Overall
CADD	23.9	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 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,882 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.Val352Phe
Coding: c.1054G>T
MANE Select: NM_000384
dbSNP: rs1572799173
Type: single nucleotide variant
Location: chr2:21033369 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 352: the vitellogenin domain

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

Similar variants

APOB p.Val352Ile Uncertain significance ★ ⚠ 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-val352phe (accessed [today's date]).

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