Is ANAPC2 p.Pro688Ala (c.2062C>G) pathogenic?

ANAPC2 p.Pro688Ala (c.2062C>G) is classified Uncertain significance in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: likely benign (0.3386); Very rare (popmax 0.00226%, eas).

How common is ANAPC2 p.Pro688Ala (c.2062C>G) in the general population?

ANAPC2 p.Pro688Ala (c.2062C>G) is very rare (popmax 0.00226%, eas) (gnomAD).

What do computational predictors say about ANAPC2 p.Pro688Ala (c.2062C>G)?

AlphaMissense predicts likely benign (score 0.3386) — an in-silico prediction, not a clinical call.

ANAPC2 p.Pro688Ala

c.2062C>G · VCV3862412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00226%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3386	likely benign
REVEL	0.539	indeterminate
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 8,277 bp · p 2.8e-12 · regional, not allelic
Overall
CADD	25.9	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 0.00226% East Asian · 1/44,208 alleles

Overall 6.9e-05% 1/1,448,918 alleles · very rare

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: ANAPC2
Protein: p.Pro688Ala
Coding: c.2062C>G
MANE Select: NM_013366
Type: single nucleotide variant
Location: chr9:137175431 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 23 PDB
Residue 688: the 'cullin homology' region

Full ANAPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANAPC2 p.Ala664= Benign/Likely benign ★★ same type
ANAPC2 p.Tyr509= Benign ★★ same type
ANAPC2 p.Ala36Val Uncertain significance ★ ⚠ same type
ANAPC2 p.Ala380Asp Uncertain significance ★ ⚠ same type
ANAPC2 p.Ala4Val Uncertain significance ★ ⚠ same type
ANAPC2 p.Arg121Leu Uncertain significance ★ ⚠ same type
ANAPC2 p.Arg210His Uncertain significance ★ ⚠ same type
ANAPC2 p.Arg270Gln 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/anapc2-p-pro688ala (accessed [today's date]).

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