Is APOM p.Arg89Pro (c.266G>C) pathogenic?

APOM p.Arg89Pro (c.266G>C) is classified Uncertain significance in APOM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9766); Ultra-rare (popmax 0.0107%, afr).

How common is APOM p.Arg89Pro (c.266G>C) in the general population?

APOM p.Arg89Pro (c.266G>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about APOM p.Arg89Pro (c.266G>C)?

AlphaMissense predicts likely pathogenic (score 0.9766) — an in-silico prediction, not a clinical call.

APOM p.Arg89Pro

c.266G>C · rs369056786 · VCV2251705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9766	likely pathogenic · top 2% in APOM
REVEL	0.392	indeterminate
SaProt	LLR -13.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,119 bp · p 0.03 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,886 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,613,230 alleles · ultra-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: APOM
Protein: p.Arg89Pro
Coding: c.266G>C
MANE Select: NM_019101
dbSNP: rs369056786
Type: single nucleotide variant
Location: chr6:31656623 (GRCh38)
Gene constraint: LOEUF 1.437 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.61 · 3 PDB
Residue 89: a β-strand; a disulfide bond

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

Similar variants

APOM p.Asn135Ile Uncertain significance ★ ⚠ same type
APOM p.Glu59Lys Uncertain significance ★ ⚠ same type
APOM p.Gly140Arg Uncertain significance ★ ⚠ same type
APOM p.Leu104Pro Uncertain significance ★ same type
APOM p.Met80Ile Uncertain significance ★ ⚠ same type
APOM p.Pro24Thr Uncertain significance ★ ⚠ same type
APOM p.Pro79Leu Uncertain significance ★ ⚠ same type
APOM p.Tyr141Asn 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/apom-p-arg89pro (accessed [today's date]).

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