Is APC2 p.Pro1501= (c.4503C>T) pathogenic?

APC2 p.Pro1501= (c.4503C>T) is classified Benign in APC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 7.82%, mid) — too common for a highly-penetrant pathogenic allele.

APC2 p.Pro1501=

Q: How common is APC2 p.Pro1501= (c.4503C>T) in the general population?

APC2 p.Pro1501= (c.4503C>T) is common (popmax 7.82%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4503C>T · rs61749994 · VCV1548346

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.82%, mid) — too common for a highly-penetrant pathogenic allele

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 0.97	GERP -1.7, phastCons 1
Overall
CADD	7.735	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.82% Middle Eastern · 403/5,152 alleles

Filtering AF 7.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.94%

Overall 4.31% 63,299/1,470,238 alleles · common exomes 57,269/1,317,940 · genomes 6,030/152,298 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	7.82%	13
Ashkenazi Jewishnot grpmax-eligible	6.77%	15
South Asian	4.97%	20
European (non-Finnish)	4.51%	22
Remaining individualsnot grpmax-eligible	4.32%	23
Finnishnot grpmax-eligible	4.01%	25
African / African-American	2.79%	36
Admixed American	2.74%	37
Amishnot grpmax-eligible	1.75%	57
East Asian	0.038%	2,628

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: APC2
Protein: p.Pro1501=
Coding: c.4503C>T
MANE Select: NM_005883
dbSNP: rs61749994
Type: single nucleotide variant
Location: chr19:1467804 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 1501: the '5 x 20 aa approximate repeat of f-x-v-e-x-t-p-x-c-f-s-r-x-s-s-l-s-s-l-s' region; the 'interaction with ctnnb1' region; a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APC2 p.Pro1501Ser Uncertain significance ★ ⚠ same residue
APC2 p.Ala1059Glu Uncertain significance ★★ ⚠ same type
APC2 p.Ala1103Thr Uncertain significance ★★ ⚠ same type
APC2 p.Ala1116Val Uncertain significance ★★ ⚠ same type
APC2 p.Ala126Ser Uncertain significance ★★ ⚠ same type
APC2 p.Ala1311Thr Uncertain significance ★★ ⚠ same type
APC2 p.Ala1359Val Uncertain significance ★★ ⚠ same type
APC2 p.Ala1438Thr Uncertain significance ★★ ⚠ same type

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/apc2-p-pro1501 (accessed [today's date]).

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