Is APC p.Arg94Pro (c.281G>C) pathogenic?

APC p.Arg94Pro (c.281G>C) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-03). AlphaMissense: likely benign (0.1782); Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg94Pro (c.281G>C)?

APC p.Arg94Pro (c.281G>C) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Arg94Pro (c.281G>C) in the general population?

APC p.Arg94Pro (c.281G>C) is absent from gnomAD v4.1 (gnomAD).

How is Familial adenomatous polyposis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about APC p.Arg94Pro (c.281G>C)?

AlphaMissense predicts likely benign (score 0.1782) — an in-silico prediction, not a clinical call.

APC p.Arg94Pro

c.281G>C · rs774229223 · VCV1478924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.1782	likely benign
REVEL	0.531	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: APC
Protein: p.Arg94Pro
Coding: c.281G>C
MANE Select: NM_000038
dbSNP: rs774229223
Type: single nucleotide variant
Location: chr5:112767249 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

familial adenomatous polyposis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Arg94Cys Uncertain significance ★★ same residue
APC p.Arg94Gly Uncertain significance ★★ same residue
APC p.Arg94His Uncertain significance ★★ same residue
APC p.Arg94= Benign/Likely benign ★★ same residue
APC p.Arg94Ser Conflicting classifications of pathogenicity ★ same residue
APC p.Arg94delinsLeuGluGluIleGlyHisHisHisSerGlnTer Pathogenic ★ same residue
APC p.Arg94fs Likely pathogenic ★ same residue
APC c.1312+3A>C Likely 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/apc-p-arg94pro (accessed [today's date]).

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