Is ANAPC2 p.Pro582Ser (c.1744C>T) pathogenic?

ANAPC2 p.Pro582Ser (c.1744C>T) is classified Uncertain significance in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely benign (0.086); Ultra-rare (popmax 0.0604%, sas).

How common is ANAPC2 p.Pro582Ser (c.1744C>T) in the general population?

ANAPC2 p.Pro582Ser (c.1744C>T) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about ANAPC2 p.Pro582Ser (c.1744C>T)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

ANAPC2 p.Pro582Ser

c.1744C>T · rs572454732 · VCV2489184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -7.85	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 8.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 8,277 bp · p 2.8e-12 · regional, not allelic
Overall
CADD	19.2	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

Grpmax group 0.0604% South Asian · 55/91,080 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.00366% 59/1,613,236 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,656
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)	8.47e-05%	1,179,988

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.Pro582Ser
Coding: c.1744C>T
MANE Select: NM_013366
dbSNP: rs572454732
Type: single nucleotide variant
Location: chr9:137180327 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 23 PDB
Residue 582: 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-pro582ser (accessed [today's date]).

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