Is APC p.Gln1237= (c.3711G>A) pathogenic?

APC p.Gln1237= (c.3711G>A) is classified Benign/Likely benign in APC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-29). Ultra-rare (popmax 0.0198%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with APC p.Gln1237= (c.3711G>A)?

APC p.Gln1237= (c.3711G>A) is associated with hereditary neoplastic syndrome, familial adenomatous polyposis 1 (ClinVar).

How common is APC p.Gln1237= (c.3711G>A) in the general population?

APC p.Gln1237= (c.3711G>A) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

APC p.Gln1237=

c.3711G>A · rs756939805 · VCV416754

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

hereditary neoplastic syndrome

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 -2.6	GERP -5.9
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,080 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.0013% 19/1,461,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,060
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Gln1237=
Coding: c.3711G>A
MANE Select: NM_000038
dbSNP: rs756939805
Type: single nucleotide variant
Location: chr5:112839305 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1237: the 'responsible for down-regulation through a process mediated by direct ubiquitination' region; the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial adenomatous polyposis 1

Similar variants

APC p.Gln1237Ter Pathogenic ★★ same residue
APC p.Gln1237Arg Uncertain significance ★★ same residue
APC p.Gln1237His Uncertain significance ★★ same residue
APC p.Gln1237Leu Uncertain significance ★★ same residue
APC p.Gln1237Glu Uncertain significance ★ same residue
APC p.Gln1237fs Pathogenic ★ 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-gln1237 (accessed [today's date]).

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