Is APOC2 p.Thr86Arg (c.257C>G) pathogenic?

APOC2 p.Thr86Arg (c.257C>G) is classified Uncertain significance in APOC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.6062); Very rare (popmax 0.004%, afr); Associated with Cardiovascular phenotype.

What condition is associated with APOC2 p.Thr86Arg (c.257C>G)?

APOC2 p.Thr86Arg (c.257C>G) is associated with Cardiovascular phenotype, familial apolipoprotein C-II deficiency (ClinVar).

How common is APOC2 p.Thr86Arg (c.257C>G) in the general population?

APOC2 p.Thr86Arg (c.257C>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about APOC2 p.Thr86Arg (c.257C>G)?

AlphaMissense predicts likely pathogenic (score 0.6062) — an in-silico prediction, not a clinical call.

APOC2 p.Thr86Arg

c.257C>G · rs199687805 · VCV2447633

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6062	likely pathogenic
REVEL	0.31	indeterminate
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.2, phastCons 0.053
Regional constraint	o/e 0.94	unconstrained · MANE · 767 bp · p 0.48 · regional, not allelic
Overall
CADD	17.57	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 0.004% African / African-American · 3/74,928 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,976
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Thr86Arg
Coding: c.257C>G
MANE Select: NM_000483
dbSNP: rs199687805
Type: single nucleotide variant
Location: chr19:44949200 (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 86: a β-strand; the 'lipoprotein lipase cofactor' region

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

Also linked: familial apolipoprotein C-II deficiency

Similar variants

APOC2 p.Gln25Ter Likely pathogenic ★★ same condition
APOC2 p.Gln92Ter Pathogenic/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.Val67Ile Uncertain significance ★★ ⚠ same condition
APOC2 c.56-4G>C Benign ★★ 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-thr86arg (accessed [today's date]).

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