Is CDCA3 p.Pro114Gln (c.341C>A) pathogenic?

CDCA3 p.Pro114Gln (c.341C>A) is classified Uncertain significance in CDCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely benign (0.077); Very rare (popmax 0.00551%, sas).

How common is CDCA3 p.Pro114Gln (c.341C>A) in the general population?

CDCA3 p.Pro114Gln (c.341C>A) is very rare (popmax 0.00551%, sas) (gnomAD).

What do computational predictors say about CDCA3 p.Pro114Gln (c.341C>A)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

CDCA3 p.Pro114Gln

c.341C>A · rs781809709 · VCV3141009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.017	GERP -5.1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,906 bp · p 0.045 · regional, not allelic
Overall
CADD	0.115	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 0.00551% South Asian · 5/90,776 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.000411% 6/1,458,514 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00551%	18,155
European (non-Finnish)	8.49e-05%	1,177,706

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.Pro114Gln
Coding: c.341C>A
MANE Select: NM_031299
dbSNP: rs781809709
Type: single nucleotide variant
Location: chr12:6849768 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.01
Residue 114: the 'disordered' region; the 'f-box-like' region

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

Similar variants

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GNB3 p.Arg251Cys Uncertain significance ★★ ⚠ same type
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GNB3 p.Arg283Cys Uncertain significance ★★ ⚠ same type
GNB3 p.Arg283His Uncertain significance ★★ ⚠ same type
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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-pro114gln (accessed [today's date]).

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