Is APC2 p.Ala704Val (c.2111C>T) pathogenic?

APC2 p.Ala704Val (c.2111C>T) is classified Uncertain significance in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely benign (0.0965); No allele count reported in gnomAD v4.1 (AN 1,547,194).

How common is APC2 p.Ala704Val (c.2111C>T) in the general population?

APC2 p.Ala704Val (c.2111C>T) is no allele count reported in gnomAD v4.1 (AN 1,547,194) (gnomAD).

What do computational predictors say about APC2 p.Ala704Val (c.2111C>T)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

APC2 p.Ala704Val

c.2111C>T · rs2083991537 · VCV2120670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,547,194)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -7.77	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 0.81	GERP 0.27, phastCons 0.22
Overall
CADD	18.58	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 1,547,194). 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.Ala704Val
Coding: c.2111C>T
MANE Select: NM_005883
dbSNP: rs2083991537
Type: single nucleotide variant
Location: chr19:1465412 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 704: 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-ala704val (accessed [today's date]).

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