Is APOC2 p.Arg72Thr (c.215G>C) pathogenic?

APOC2 p.Arg72Thr (c.215G>C) is classified Uncertain significance in APOC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely pathogenic (0.6961); Absent from gnomAD v4.1.

How common is APOC2 p.Arg72Thr (c.215G>C) in the general population?

APOC2 p.Arg72Thr (c.215G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOC2 p.Arg72Thr (c.215G>C)?

AlphaMissense predicts likely pathogenic (score 0.6961) — an in-silico prediction, not a clinical call.

APOC2 p.Arg72Thr

c.215G>C · rs1475941193 · VCV2736904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6961	likely pathogenic
REVEL	0.717	pathogenic-leaning
SaProt	LLR -8.40	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.82	donor loss · deltas
Pangolin	Δ0.83	loss · gain 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 767 bp · p 0.48 · regional, not allelic
Overall
CADD	34.0	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

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: APOC2
Protein: p.Arg72Thr
Coding: c.215G>C
MANE Select: NM_000483
dbSNP: rs1475941193
Type: single nucleotide variant
Location: chr19:44948860 (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 72: a β-strand; the 'lipid binding' region

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

Similar variants

APOC2 p.Gln25Ter Likely pathogenic ★★ same type
APOC2 p.Gln92Ter Pathogenic/Likely pathogenic ★★ same type
APOC2 p.Ala54Asp Uncertain significance ★★ ⚠ same type
APOC2 p.Ala55Thr Uncertain significance ★★ ⚠ same type
APOC2 p.Ser76Ile Uncertain significance ★★ ⚠ same type
APOC2 p.Thr23Ile Uncertain significance ★★ ⚠ same type
APOC2 p.Thr86Arg Uncertain significance ★★ ⚠ same type
APOC2 p.Val67Ile Uncertain significance ★★ ⚠ same type

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-arg72thr (accessed [today's date]).

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