Is CDCA5 p.Glu169Lys (c.505G>A) pathogenic?

CDCA5 p.Glu169Lys (c.505G>A) is classified Uncertain significance in CDCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.185); Very rare (popmax 0.00329%, sas).

How common is CDCA5 p.Glu169Lys (c.505G>A) in the general population?

CDCA5 p.Glu169Lys (c.505G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CDCA5 p.Glu169Lys (c.505G>A)?

AlphaMissense predicts likely benign (score 0.185) — an in-silico prediction, not a clinical call.

CDCA5 p.Glu169Lys

c.505G>A · rs1340393208 · VCV2251823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.185	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.27	GERP -1, phastCons 0.005
Regional constraint	o/e 0.95	unconstrained · MANE · 4,868 bp · p 0.33 · regional, not allelic
Overall
CADD	21.4	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000682% 11/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Admixed American	0.00167%	59,992
European (non-Finnish)	0.000593%	168,577

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.Glu169Lys
Coding: c.505G>A
MANE Select: NM_080668
dbSNP: rs1340393208
Type: single nucleotide variant
Location: chr11:65079526 (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.Arg148Trp Uncertain significance ★ ⚠ same type
CDCA5 p.Arg4Gly 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-glu169lys (accessed [today's date]).

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