Is CDCA3 p.Ile39Val (c.115A>G) pathogenic?

CDCA3 p.Ile39Val (c.115A>G) is classified Uncertain significance in CDCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.5847); Ultra-rare (popmax 0.011%, nfe).

How common is CDCA3 p.Ile39Val (c.115A>G) in the general population?

CDCA3 p.Ile39Val (c.115A>G) is ultra-rare (popmax 0.011%, nfe) (gnomAD).

What do computational predictors say about CDCA3 p.Ile39Val (c.115A>G)?

AlphaMissense predicts likely pathogenic (score 0.5847) — an in-silico prediction, not a clinical call.

CDCA3 p.Ile39Val

c.115A>G · rs367977966 · VCV3141006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5847	likely pathogenic
REVEL	0.17	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,906 bp · p 0.045 · regional, not allelic
Overall
CADD	25.0	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 0.011% European (non-Finnish) · 130/1,179,934 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00849% 137/1,613,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.011%	9,076
Remaining individualsnot grpmax-eligible	0.0064%	15,621
African / African-American	0.00267%	37,449
East Asian	0.00223%	44,900

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.Ile39Val
Coding: c.115A>G
MANE Select: NM_031299
dbSNP: rs367977966
Type: single nucleotide variant
Location: chr12:6850838 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.01
Residue 39: the 'disordered' region

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

Similar variants

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
GNB3 p.Arg304Cys 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-ile39val (accessed [today's date]).

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