Is CDCA4 p.Arg34Gln (c.101G>A) pathogenic?

CDCA4 p.Arg34Gln (c.101G>A) is classified Uncertain significance in CDCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.7097); Ultra-rare (popmax 0.0559%, afr).

How common is CDCA4 p.Arg34Gln (c.101G>A) in the general population?

CDCA4 p.Arg34Gln (c.101G>A) is ultra-rare (popmax 0.0559%, afr) (gnomAD).

What do computational predictors say about CDCA4 p.Arg34Gln (c.101G>A)?

AlphaMissense predicts likely pathogenic (score 0.7097) — an in-silico prediction, not a clinical call.

CDCA4 p.Arg34Gln

c.101G>A · rs145318953 · VCV2511132

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7097	likely pathogenic
REVEL	0.233	benign-leaning
SaProt	LLR -12.85	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 722 bp · p 0.12 · regional, not allelic
Overall
CADD	23.9	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 0.0559% African / African-American · 42/75,070 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00297% 48/1,613,882 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0559%	1,787
Admixed American	0.00167%	60,024
Finnishnot grpmax-eligible	0.00157%	63,688
South Asian	0.0011%	91,086
European (non-Finnish)	0.000254%	393,346

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: CDCA4
Protein: p.Arg34Gln
Coding: c.101G>A
MANE Select: NM_017955
dbSNP: rs145318953
Type: single nucleotide variant
Location: chr14:105011829 (GRCh38)
Gene constraint: LOEUF 1.807 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 64.15
Residue 34: the serta domain

Full CDCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA4 p.Ala135Val Uncertain significance ★ ⚠ same type
CDCA4 p.Ala145Pro Uncertain significance ★ ⚠ same type
CDCA4 p.Arg103His Uncertain significance ★ ⚠ same type
CDCA4 p.Arg152Gly Uncertain significance ★ ⚠ same type
CDCA4 p.Arg80Cys Uncertain significance ★ ⚠ same type
CDCA4 p.Arg80Leu Uncertain significance ★ ⚠ same type
CDCA4 p.Arg89Trp Uncertain significance ★ ⚠ same type
CDCA4 p.Arg94His 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/cdca4-p-arg34gln (accessed [today's date]).

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