Is APC2 p.Asp1490= (c.4470C>T) pathogenic?

APC2 p.Asp1490= (c.4470C>T) is classified Benign in APC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). Common (popmax 8.1%, afr) — too common for a highly-penetrant pathogenic allele.

APC2 p.Asp1490=

Q: How common is APC2 p.Asp1490= (c.4470C>T) in the general population?

APC2 p.Asp1490= (c.4470C>T) is common (popmax 8.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4470C>T · rs265272 · VCV1343931

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.1%, afr) — 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 -16	GERP -1.8
Overall
CADD	0.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.1% African / African-American · 5,431/67,034 alleles

Filtering AF 7.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.85%

Overall 0.426% 6,100/1,430,686 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.1%	12
Admixed American	0.609%	164
Remaining individualsnot grpmax-eligible	0.576%	174
Middle Eastern	0.419%	238
South Asian	0.013%	7,674
European (non-Finnish)	0.00893%	11,204
East Asian	0.00551%	18,149
Ashkenazi Jewishnot grpmax-eligible	0.00452%	22,122

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.Asp1490=
Coding: c.4470C>T
MANE Select: NM_005883
dbSNP: rs265272
Type: single nucleotide variant
Location: chr19:1467771 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 1490: 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; the 'disordered' 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.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
APC2 p.Ala1492Glu 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-asp1490 (accessed [today's date]).

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