Is ANAPC2 p.Ala36Val (c.107C>T) pathogenic?

ANAPC2 p.Ala36Val (c.107C>T) is classified Uncertain significance in ANAPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: ambiguous (0.492); Very rare (popmax 0.00466%, nfe).

How common is ANAPC2 p.Ala36Val (c.107C>T) in the general population?

ANAPC2 p.Ala36Val (c.107C>T) is very rare (popmax 0.00466%, nfe) (gnomAD).

What do computational predictors say about ANAPC2 p.Ala36Val (c.107C>T)?

AlphaMissense predicts ambiguous (score 0.492) — an in-silico prediction, not a clinical call.

ANAPC2 p.Ala36Val

c.107C>T · VCV4094464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.492	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -4.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP -1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 4,832 bp · p 0.00015 · regional, not allelic
Overall
CADD	19.4	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 0.00466% European (non-Finnish) · 55/1,179,146 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00361% 58/1,607,736 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00466%	21,439
Admixed American	0.00334%	29,932
African / African-American	0.00133%	74,918

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.Ala36Val
Coding: c.107C>T
MANE Select: NM_013366
Type: single nucleotide variant
Location: chr9:137188426 (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.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
ANAPC2 p.Arg270Trp 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-ala36val (accessed [today's date]).

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