Is CDCA3 p.Gly72Arg (c.214G>C) pathogenic?

CDCA3 p.Gly72Arg (c.214G>C) is classified Uncertain significance in CDCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely pathogenic (0.9261); Very rare (popmax 0.00534%, afr).

How common is CDCA3 p.Gly72Arg (c.214G>C) in the general population?

CDCA3 p.Gly72Arg (c.214G>C) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CDCA3 p.Gly72Arg (c.214G>C)?

AlphaMissense predicts likely pathogenic (score 0.9261) — an in-silico prediction, not a clinical call.

CDCA3 p.Gly72Arg

c.214G>C · VCV3488568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9261	likely pathogenic · top 3% in CDCA3
REVEL	0.397	indeterminate
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,906 bp · p 0.045 · regional, not allelic
Overall
CADD	27.5	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 0.00534% African / African-American · 4/74,888 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,722
European (non-Finnish)	0.000254%	393,343

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: CDCA3
Protein: p.Gly72Arg
Coding: c.214G>C
MANE Select: NM_031299
Type: single nucleotide variant
Location: chr12:6850503 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.01
Residue 72: the 'disordered' region

Full CDCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA3 p.Gly72Asp Uncertain significance ★ ⚠ same residue
GNB3 p.Ala248Ser Uncertain significance ★★ ⚠ same type
GNB3 p.Ala248Thr Uncertain significance ★★ ⚠ same type
GNB3 p.Ala287Ser Uncertain significance ★★ ⚠ same type
GNB3 p.Arg251Cys Uncertain significance ★★ ⚠ same type
GNB3 p.Arg251His Uncertain significance ★★ ⚠ same type
GNB3 p.Arg283Cys Uncertain significance ★★ ⚠ same type
GNB3 p.Arg283His 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/cdca3-p-gly72arg (accessed [today's date]).

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