Is APC2 p.Arg2184Pro (c.6551G>C) pathogenic?

APC2 p.Arg2184Pro (c.6551G>C) is classified Conflicting classifications of pathogenicity in APC2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.28); Rare (popmax 0.292%, amr); Associated with Inborn genetic diseases.

What condition is associated with APC2 p.Arg2184Pro (c.6551G>C)?

APC2 p.Arg2184Pro (c.6551G>C) is associated with Inborn genetic diseases (ClinVar).

How common is APC2 p.Arg2184Pro (c.6551G>C) in the general population?

APC2 p.Arg2184Pro (c.6551G>C) is rare (popmax 0.292%, amr) (gnomAD).

What do computational predictors say about APC2 p.Arg2184Pro (c.6551G>C)?

AlphaMissense predicts likely benign (score 0.28) — an in-silico prediction, not a clinical call.

APC2 p.Arg2184Pro

c.6551G>C · rs763459814 · VCV2061067

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.28 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.292%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.28	likely benign
REVEL	0.556	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.93, phastCons 1
Overall
CADD	26.0	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

Grpmax group 0.292% Admixed American · 145/49,612 alleles

Filtering AF 0.253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.239%

Overall 0.0101% 153/1,519,550 alleles · rare exomes 138/1,367,688 · genomes 15/151,862 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.292%	342
Remaining individualsnot grpmax-eligible	0.00675%	14,807
South Asian	0.00361%	27,681
European (non-Finnish)	8.77e-05%	1,140,892

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: APC2
Protein: p.Arg2184Pro
Coding: c.6551G>C
MANE Select: NM_005883
dbSNP: rs763459814
Type: single nucleotide variant
Location: chr19:1469852 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 2184: the 'disordered' region; a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APC2 p.Arg2184Gly Uncertain significance ★ ⚠ same residue
APC2 p.Ala1059Glu Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1103Thr Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1116Val Uncertain significance ★★ ⚠ same condition
APC2 p.Ala126Ser Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1311Thr Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1359Val Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1438Thr 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/apc2-p-arg2184pro (accessed [today's date]).

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