Is APC p.Pro41Arg (c.122C>G) pathogenic?

APC p.Pro41Arg (c.122C>G) is classified Uncertain significance in APC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). Absent from gnomAD v4.1; Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Pro41Arg (c.122C>G)?

APC p.Pro41Arg (c.122C>G) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Pro41Arg (c.122C>G) in the general population?

APC p.Pro41Arg (c.122C>G) 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.

APC p.Pro41Arg

c.122C>G · rs1057517584 · VCV1034624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.189	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -2.2
Overall
CADD	7.595	PHRED · no single calibrated threshold — expert panels disagree

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.Pro41Arg
Coding: c.122C>G
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs1057517584
Type: single nucleotide variant
Location: chr5:112707839 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 41: an α-helix

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.Ala41= Likely benign ★★★ same residue
APC p.Ala41Val Uncertain significance ★★ ⚠ same residue
APC p.Ala41Glu Uncertain significance ★ same residue
APC p.Ala41Ser Uncertain significance ★ same residue
APC p.Ala41Thr Conflicting classifications of pathogenicity ★ same residue
APC p.Pro41= Uncertain significance ★ same residue
APC p.Pro41Ala Conflicting classifications of pathogenicity ★ same residue
APC p.Pro41Ser Uncertain significance ★ same residue

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-pro41arg (accessed [today's date]).

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