Is ANAPC2 p.Ser697= (c.2091C>T) pathogenic?

ANAPC2 p.Ser697= (c.2091C>T) is classified Likely benign in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Rare (popmax 0.121%, amr).

How common is ANAPC2 p.Ser697= (c.2091C>T) in the general population?

ANAPC2 p.Ser697= (c.2091C>T) is rare (popmax 0.121%, amr) (gnomAD).

ANAPC2 p.Ser697=

c.2091C>T · rs140009201 · VCV2659813

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.121%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -2.9
Overall
CADD	0.293	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.121% Admixed American · 72/59,674 alleles

Filtering AF 0.0997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0978%

Overall 0.087% 1,400/1,608,606 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.149%	670
Admixed Americangrpmax	0.121%	829
European (non-Finnish)	0.105%	956
Remaining individualsnot grpmax-eligible	0.0498%	2,007
African / African-American	0.0187%	5,354
Finnishnot grpmax-eligible	0.0081%	12,343
South Asian	0.0011%	90,548

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser697=
Coding: c.2091C>T
MANE Select: NM_013366
dbSNP: rs140009201
Type: single nucleotide variant
Location: chr9:137175402 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 23 PDB
Residue 697: the 'cullin homology' region; an α-helix; a modified residue (phosphoserine)

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-ser697 (accessed [today's date]).

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