Is APC2 p.Pro1501Ser (c.4501C>T) pathogenic?

APC2 p.Pro1501Ser (c.4501C>T) is classified Uncertain significance in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely pathogenic (0.7947); Very rare (popmax 0.00732%, amr); Associated with Inborn genetic diseases.

What condition is associated with APC2 p.Pro1501Ser (c.4501C>T)?

APC2 p.Pro1501Ser (c.4501C>T) is associated with Inborn genetic diseases (ClinVar).

How common is APC2 p.Pro1501Ser (c.4501C>T) in the general population?

APC2 p.Pro1501Ser (c.4501C>T) is very rare (popmax 0.00732%, amr) (gnomAD).

What do computational predictors say about APC2 p.Pro1501Ser (c.4501C>T)?

AlphaMissense predicts likely pathogenic (score 0.7947) — an in-silico prediction, not a clinical call.

APC2 p.Pro1501Ser

c.4501C>T · rs977495041 · VCV3127738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00732%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7947	likely pathogenic
REVEL	0.547	indeterminate
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.89, phastCons 1
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00732% Admixed American · 3/40,998 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000274% 4/1,462,048 alleles · very rare exomes 1/1,309,858 · genomes 3/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00732%	13,666
Remaining individualsnot grpmax-eligible	0.00177%	56,410

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.Pro1501Ser
Coding: c.4501C>T
MANE Select: NM_005883
dbSNP: rs977495041
Type: single nucleotide variant
Location: chr19:1467802 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APC2 p.Pro1501= Benign ★★ same residue
APC2 p.Ala1059Glu Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1103Thr Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1116Val Uncertain significance ★★ ⚠ same condition
APC2 p.Ala126Ser Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1311Thr Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1359Val Uncertain significance ★★ ⚠ same condition
APC2 p.Ala1438Thr Uncertain significance ★★ ⚠ 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/apc2-p-pro1501ser (accessed [today's date]).

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