Is APOC2 p.Trp48Arg (c.142T>C) pathogenic?

APOC2 p.Trp48Arg (c.142T>C) is classified Pathogenic in APOC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1993-06-30). AlphaMissense: likely pathogenic (0.8658); Very rare (popmax 0.00669%, eas); Associated with APOLIPOPROTEIN C-II (WAKAYAMA).

What condition is associated with APOC2 p.Trp48Arg (c.142T>C)?

APOC2 p.Trp48Arg (c.142T>C) is associated with APOLIPOPROTEIN C-II (WAKAYAMA), familial apolipoprotein C-II deficiency (ClinVar).

How common is APOC2 p.Trp48Arg (c.142T>C) in the general population?

APOC2 p.Trp48Arg (c.142T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about APOC2 p.Trp48Arg (c.142T>C)?

AlphaMissense predicts likely pathogenic (score 0.8658) — an in-silico prediction, not a clinical call.

APOC2 p.Trp48Arg

c.142T>C · rs120074115 · VCV2583

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

APOLIPOPROTEIN C-II (WAKAYAMA)

Computational evidence

Protein change
AlphaMissense	0.8658	likely pathogenic ✓ concordant with ClinVar · top 7% in APOC2
REVEL	0.782	moderately pathogenic-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 767 bp · p 0.48 · regional, not allelic
Overall
CADD	25.6	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 0.00669% East Asian · 3/44,876 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000205% 3/1,461,870 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.Trp48Arg
Coding: c.142T>C
MANE Select: NM_000483
dbSNP: rs120074115
Type: single nucleotide variant
Location: chr19:44948787 (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 48: an α-helix; a UniProt-annotated variant site (in hlpp1b; variant wakayama)

Full APOC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

APOLIPOPROTEIN C-II (WAKAYAMA)

Also linked: familial apolipoprotein C-II deficiency

Similar variants

APOC2 p.Gln92Ter Pathogenic/Likely pathogenic ★★ same condition
APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same condition
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same condition
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same condition
APOC2 c.56-4G>C Benign ★★ same condition
APOC2 p.Glu60Lys Benign/Likely benign ★★ same condition
APOC2 c.216-1G>A 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/apoc2-p-trp48arg (accessed [today's date]).

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