Is APC p.Arg31= (c.91A>C) pathogenic?

APC p.Arg31= (c.91A>C) is classified Uncertain significance in APC (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-08). Very rare (popmax 0.00979%, sas); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg31= (c.91A>C)?

APC p.Arg31= (c.91A>C) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Arg31= (c.91A>C) in the general population?

APC p.Arg31= (c.91A>C) is very rare (popmax 0.00979%, sas) (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.Arg31=

c.91A>C · rs1302045127 · VCV537597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00979%, sas)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.2	GERP -3.9
Overall
CADD	0.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00979% South Asian · 8/81,724 alleles

Filtering AF 0.0048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.000584% 8/1,370,578 alleles · very rare exomes 8/1,218,342 · genomes 0/152,236 · joint denominator

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: APC
Protein: p.Arg31=
Coding: c.91A>C
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs1302045127
Type: single nucleotide variant
Location: chr5:112707808 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 31: 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.Arg31Gly Uncertain significance ★★ same residue
APC p.Arg31Lys Uncertain significance ★ same residue
APC p.Arg31Ser Uncertain significance ★ same residue
APC p.Ser31= Benign ★ same residue
APC p.Ser31Cys Uncertain significance ★★ same residue
APC p.Ser31Phe Uncertain significance ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G 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-arg31 (accessed [today's date]).

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