Is CDC20 p.His112Gln (c.336T>A) pathogenic?

CDC20 p.His112Gln (c.336T>A) is classified Uncertain significance in CDC20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely benign (0.0885); Very rare (popmax 0.00602%, nfe).

How common is CDC20 p.His112Gln (c.336T>A) in the general population?

CDC20 p.His112Gln (c.336T>A) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about CDC20 p.His112Gln (c.336T>A)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

CDC20 p.His112Gln

c.336T>A · rs1225329364 · VCV2277846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.55	GERP -1.3, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 526 bp · p 0.00099 · regional, not allelic
Overall
CADD	17.78	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 0.00602% European (non-Finnish) · 71/1,180,006 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00446% 72/1,613,678 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
African / African-American	0.00134%	74,872

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: CDC20
Protein: p.His112Gln
Coding: c.336T>A
MANE Select: NM_001255
dbSNP: rs1225329364
Type: single nucleotide variant
Location: chr1:43359730 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.39 · 17 PDB
Residue 112: an α-helix

Full CDC20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC20 p.Glu484= Benign ★★ same type
CDC20 p.Val361Ile Benign/Likely benign ★★ same type
CDC20 p.Cys364Ter Likely pathogenic ★ same type
CDC20 c.556+1G>T Conflicting classifications of pathogenicity ★ same type
CDC20 p.Ala140Val Uncertain significance ★ ⚠ same type
CDC20 p.Ala242Val Uncertain significance ★ ⚠ same type
CDC20 p.Ala461Thr Uncertain significance ★ ⚠ same type
CDC20 p.Arg162Gly 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/cdc20-p-his112gln (accessed [today's date]).

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