Is APOC2 p.Val40Gly (c.119T>G) pathogenic?

APOC2 p.Val40Gly (c.119T>G) is classified Uncertain significance in APOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-24). AlphaMissense: ambiguous (0.4305); Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOC2 p.Val40Gly (c.119T>G)?

APOC2 p.Val40Gly (c.119T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is APOC2 p.Val40Gly (c.119T>G) in the general population?

APOC2 p.Val40Gly (c.119T>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about APOC2 p.Val40Gly (c.119T>G)?

AlphaMissense predicts ambiguous (score 0.4305) — an in-silico prediction, not a clinical call.

APOC2 p.Val40Gly

c.119T>G · VCV3308425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4305	ambiguous
REVEL	0.566	indeterminate
SaProt	LLR -11.18	damaging
Splicing
SpliceAI	Δ0.36	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 767 bp · p 0.48 · regional, not allelic
Overall
CADD	23.5	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 0.000254% European (non-Finnish) · 3/1,180,010 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,884 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: APOC2
Protein: p.Val40Gly
Coding: c.119T>G
MANE Select: NM_000483
Type: single nucleotide variant
Location: chr19:44948764 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 4 PDB
Residue 40: an α-helix

Full APOC2 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

APOC2 p.Val40Leu Uncertain significance ★ ⚠ same residue
APOC2 p.Gln25Ter Likely pathogenic ★★ same condition
APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same condition
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same condition
APOC2 p.Ser76Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same condition
APOC2 p.Val67Ile 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/apoc2-p-val40gly (accessed [today's date]).

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