Is ANAPC2 p.Leu729Pro (c.2186T>C) pathogenic?

ANAPC2 p.Leu729Pro (c.2186T>C) is classified Uncertain significance in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-14). AlphaMissense: ambiguous (0.4179); Absent from gnomAD v4.1.

How common is ANAPC2 p.Leu729Pro (c.2186T>C) in the general population?

ANAPC2 p.Leu729Pro (c.2186T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANAPC2 p.Leu729Pro (c.2186T>C)?

AlphaMissense predicts ambiguous (score 0.4179) — an in-silico prediction, not a clinical call.

ANAPC2 p.Leu729Pro

c.2186T>C · rs1834184643 · VCV3117805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4179 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4179	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -7.59	tolerated
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	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANAPC2
Protein: p.Leu729Pro
Coding: c.2186T>C
MANE Select: NM_013366
dbSNP: rs1834184643
Type: single nucleotide variant
Location: chr9:137175307 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 23 PDB

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-leu729pro (accessed [today's date]).

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