Is APC2 p.Pro2294Ser (c.6880C>T) pathogenic?

APC2 p.Pro2294Ser (c.6880C>T) is classified Uncertain significance in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0844); No allele count reported in gnomAD v4.1 (AN 1,601,456); Associated with Inborn genetic diseases.

What condition is associated with APC2 p.Pro2294Ser (c.6880C>T)?

APC2 p.Pro2294Ser (c.6880C>T) is associated with Inborn genetic diseases (ClinVar).

How common is APC2 p.Pro2294Ser (c.6880C>T) in the general population?

APC2 p.Pro2294Ser (c.6880C>T) is no allele count reported in gnomAD v4.1 (AN 1,601,456) (gnomAD).

What do computational predictors say about APC2 p.Pro2294Ser (c.6880C>T)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

APC2 p.Pro2294Ser

c.6880C>T · VCV4122492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,456)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -0.2, phastCons 0.004
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,456). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APC2
Protein: p.Pro2294Ser
Coding: c.6880C>T
MANE Select: NM_005883
Type: single nucleotide variant
Location: chr19:1470181 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 2294: 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.Pro2294Ala Uncertain significance ★ ⚠ same residue
APC2 p.Pro2294Gln Uncertain significance ★ ⚠ 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

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-pro2294ser (accessed [today's date]).

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