Is APC p.Arg45His (c.134G>A) pathogenic?

APC p.Arg45His (c.134G>A) is classified Uncertain significance in APC (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-08). No allele count reported in gnomAD v4.1 (AN 1,370,212); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Arg45His (c.134G>A)?

APC p.Arg45His (c.134G>A) is associated with familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Arg45His (c.134G>A) in the general population?

APC p.Arg45His (c.134G>A) is no allele count reported in gnomAD v4.1 (AN 1,370,212) (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.Arg45His

c.134G>A · rs1004213568 · VCV548852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,370,212)

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.151	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.042, phastCons 0.14
Overall
CADD	14.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,370,212). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APC
Protein: p.Arg45His
Coding: c.134G>A
MANE Select: NM_000038 · reported on NM_001127511
dbSNP: rs1004213568
Type: single nucleotide variant
Location: chr5:112707851 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 45: 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.Arg45Cys Conflicting classifications of pathogenicity ★ same residue
APC p.Arg45Gly Uncertain significance ★ same residue
APC p.Arg45Leu Uncertain significance ★ same residue
APC p.Arg45Pro Uncertain significance ★ same residue
APC p.Arg45Ser Uncertain significance ★ same residue
APC p.Lys45= Uncertain significance ★ same residue
APC p.Lys45fs Pathogenic ★★ same residue
APC p.Lys45Thr 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-arg45his (accessed [today's date]).

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