Is CDCA4 p.Asp163Glu (c.489T>A) pathogenic?

CDCA4 p.Asp163Glu (c.489T>A) is classified Uncertain significance in CDCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: ambiguous (0.4081); Ultra-rare (popmax 0.0783%, amr).

How common is CDCA4 p.Asp163Glu (c.489T>A) in the general population?

CDCA4 p.Asp163Glu (c.489T>A) is ultra-rare (popmax 0.0783%, amr) (gnomAD).

What do computational predictors say about CDCA4 p.Asp163Glu (c.489T>A)?

AlphaMissense predicts ambiguous (score 0.4081) — an in-silico prediction, not a clinical call.

CDCA4 p.Asp163Glu

c.489T>A · VCV3488570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4081 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0783%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4081	ambiguous
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -3.1, phastCons 0.67
Regional constraint	o/e 0.91	unconstrained · MANE · 722 bp · p 0.12 · regional, not allelic
Overall
CADD	6.103	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 0.0783% Admixed American · 47/60,018 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00297% 48/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0783%	1,277
European (non-Finnish)	8.47e-05%	1,179,999

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.Asp163Glu
Coding: c.489T>A
MANE Select: NM_017955
Type: single nucleotide variant
Location: chr14:105011441 (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.Arg89Trp 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-asp163glu (accessed [today's date]).

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