Is CDCA4 p.Arg89Trp (c.265C>T) pathogenic?

CDCA4 p.Arg89Trp (c.265C>T) is classified Uncertain significance in CDCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1199); Rare (popmax 0.115%, mid).

How common is CDCA4 p.Arg89Trp (c.265C>T) in the general population?

CDCA4 p.Arg89Trp (c.265C>T) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about CDCA4 p.Arg89Trp (c.265C>T)?

AlphaMissense predicts likely benign (score 0.1199) — an in-silico prediction, not a clinical call.

CDCA4 p.Arg89Trp

c.265C>T · rs147965891 · VCV2593694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1199 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1199	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -8.49	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 4.6	GERP 1.6, phastCons 0.97
Regional constraint	o/e 0.91	unconstrained · MANE · 722 bp · p 0.12 · regional, not allelic
Overall
CADD	21.8	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 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00378% 61/1,613,684 alleles · rare exomes 51/1,461,366 · genomes 10/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
African / African-American	0.0306%	3,263
Remaining individualsnot grpmax-eligible	0.016%	6,250
South Asian	0.00439%	22,766
Admixed American	0.00167%	60,008
European (non-Finnish)	0.00136%	73,750

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.Arg89Trp
Coding: c.265C>T
MANE Select: NM_017955
dbSNP: rs147965891
Type: single nucleotide variant
Location: chr14:105011665 (GRCh38)
Gene constraint: LOEUF 1.807 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 64.15

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.Arg34Gln Uncertain significance ★ ⚠ same type
CDCA4 p.Arg80Cys Uncertain significance ★ ⚠ same type
CDCA4 p.Arg80Leu 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-arg89trp (accessed [today's date]).

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