Is APC p.Pro1960= (c.5880G>A) pathogenic?

APC p.Pro1960= (c.5880G>A) is classified Benign in APC (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-02-04). Common (popmax 83.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with APC-Associated Polyposis Disorders.

What condition is associated with APC p.Pro1960= (c.5880G>A)?

APC p.Pro1960= (c.5880G>A) is associated with APC-Associated Polyposis Disorders, colon carcinoma, hereditary neoplastic syndrome (ClinVar).

APC p.Pro1960=

Q: How common is APC p.Pro1960= (c.5880G>A) in the general population?

APC p.Pro1960= (c.5880G>A) is common (popmax 83.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5880G>A · rs465899 · VCV42247

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

gnomAD v4.1

Common

common (popmax 83.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

APC-Associated Polyposis Disorders

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 0.15	GERP -5.1, phastCons 0.13
Overall
CADD	7.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83.8% East Asian · 37,588/44,848 alleles

Filtering AF 83.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 82.8%

Overall 62.5% 1,008,483/1,612,952 alleles · common exomes 916,872/1,460,966 · genomes 91,611/151,986 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	83.8%	1
Admixed American	71.2%	1
South Asian	71%	1
Remaining individualsnot grpmax-eligible	63.2%	2
Middle Eastern	61.7%	2
European (non-Finnish)	61.6%	2
Amishnot grpmax-eligible	61.5%	2
Ashkenazi Jewishnot grpmax-eligible	58%	2
Finnishnot grpmax-eligible	56.7%	2
African / African-American	53.2%	2

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.Pro1960=
Coding: c.5880G>A
MANE Select: NM_000038
dbSNP: rs465899
Type: single nucleotide variant
Location: chr5:112841474 (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

APC-Associated Polyposis Disorders

Also linked: colon carcinoma hereditary neoplastic syndrome familial adenomatous polyposis 1 familial colorectal cancer

Similar variants

APC p.Pro1960Ala Uncertain significance ★★ ⚠ same residue
APC p.Pro1960Ser Uncertain significance ★ ⚠ same residue
APC p.Pro1960Thr Uncertain significance ★ ⚠ same residue
APC p.Pro1960Leu Conflicting classifications of pathogenicity ★ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ same condition
APC c.1312+5G>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-pro1960 (accessed [today's date]).

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