Is ANAPC2 p.Glu19Lys (c.55G>A) pathogenic?

ANAPC2 p.Glu19Lys (c.55G>A) is classified Uncertain significance in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: likely benign (0.2966); Very rare (popmax 0.00305%, nfe).

How common is ANAPC2 p.Glu19Lys (c.55G>A) in the general population?

ANAPC2 p.Glu19Lys (c.55G>A) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about ANAPC2 p.Glu19Lys (c.55G>A)?

AlphaMissense predicts likely benign (score 0.2966) — an in-silico prediction, not a clinical call.

ANAPC2 p.Glu19Lys

c.55G>A · VCV4048972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2966	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.7	GERP -0.15, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 4,832 bp · p 0.00015 · regional, not allelic
Overall
CADD	18.22	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 0.00305% European (non-Finnish) · 36/1,179,510 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00255% 41/1,610,232 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,560
Finnishnot grpmax-eligible	0.00327%	30,587
European (non-Finnish)grpmax	0.00305%	32,764
African / African-American	0.00267%	37,452

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.Glu19Lys
Coding: c.55G>A
MANE Select: NM_013366
Type: single nucleotide variant
Location: chr9:137188478 (GRCh38)
Gene constraint: LOEUF 0.482 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 79.44 · 23 PDB
Residue 19: an α-helix

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-glu19lys (accessed [today's date]).

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