Is APC2 p.Pro1542= (c.4626G>A) pathogenic?

APC2 p.Pro1542= (c.4626G>A) is classified Benign/Likely benign in APC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-15). Rare (popmax 0.163%, sas).

How common is APC2 p.Pro1542= (c.4626G>A) in the general population?

APC2 p.Pro1542= (c.4626G>A) is rare (popmax 0.163%, sas) (gnomAD).

APC2 p.Pro1542=

c.4626G>A · rs111699814 · VCV2052979

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, sas)

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 -4.9	GERP -1.5
Overall
CADD	1.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% South Asian · 146/89,438 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.105% 1,663/1,584,704 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.283%	354
South Asiangrpmax	0.163%	613
Remaining individualsnot grpmax-eligible	0.12%	832
European (non-Finnish)	0.106%	939
Middle Eastern	0.0676%	1,480
Admixed American	0.0423%	2,365
Ashkenazi Jewishnot grpmax-eligible	0.0274%	3,644
African / African-American	0.026%	3,849
East Asian	0.0023%	43,530

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1542=
Coding: c.4626G>A
MANE Select: NM_005883
dbSNP: rs111699814
Type: single nucleotide variant
Location: chr19:1467927 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 1542: 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-pro1542 (accessed [today's date]).

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