Is APOB p.Pro3452= (c.10356T>G) pathogenic?

APOB p.Pro3452= (c.10356T>G) is classified Likely benign in APOB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with APOB p.Pro3452= (c.10356T>G)?

APOB p.Pro3452= (c.10356T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is APOB p.Pro3452= (c.10356T>G) in the general population?

APOB p.Pro3452= (c.10356T>G) is absent from gnomAD v4.1 (gnomAD).

APOB p.Pro3452=

c.10356T>G · VCV4124840

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 0.98	GERP 0.59, phastCons 0.99
Overall
CADD	6.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APOB
Protein: p.Pro3452=
Coding: c.10356T>G
MANE Select: NM_000384
Type: single nucleotide variant
Location: chr2:21006512 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3452: the 'heparin-binding' region

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.Pro3452Ala Uncertain significance ★★ same residue
APOB p.Pro3452Arg Uncertain significance ★ same residue
APOB p.Pro3452Leu Conflicting classifications of pathogenicity ★ 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

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-pro3452 (accessed [today's date]).

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