Is CDCA5 p.Arg148Trp (c.442C>T) pathogenic?

CDCA5 p.Arg148Trp (c.442C>T) is classified Uncertain significance in CDCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: ambiguous (0.4746); Very rare (popmax 0.00267%, afr).

How common is CDCA5 p.Arg148Trp (c.442C>T) in the general population?

CDCA5 p.Arg148Trp (c.442C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CDCA5 p.Arg148Trp (c.442C>T)?

AlphaMissense predicts ambiguous (score 0.4746) — an in-silico prediction, not a clinical call.

CDCA5 p.Arg148Trp

c.442C>T · VCV3998716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.4746	ambiguous
REVEL	0.499	indeterminate
SaProt	LLR -8.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,868 bp · p 0.33 · regional, not allelic
Overall
CADD	26.7	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 0.00267% African / African-American · 2/74,962 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00205% 33/1,613,248 alleles · very rare exomes 33/1,461,002 · genomes 0/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,481
European (non-Finnish)	0.00246%	40,673
South Asian	0.0022%	45,531

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: CDCA5
Protein: p.Arg148Trp
Coding: c.442C>T
MANE Select: NM_080668
Type: single nucleotide variant
Location: chr11:65079589 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04

Full CDCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA5 p.Glu123Lys Benign ★★ same type
CDCA5 p.Gly173= Benign ★★ same type
CDCA5 p.Gly179Arg Benign ★★ same type
CDCA5 p.Pro120= Benign ★★ same type
CDCA5 p.Thr105= Benign ★★ same type
CDCA5 p.Ala51Thr Uncertain significance ★ ⚠ same type
CDCA5 p.Arg4Gly Uncertain significance ★ ⚠ same type
CDCA5 p.Arg4Lys 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/cdca5-p-arg148trp (accessed [today's date]).

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