Is CDCA5 p.Val73Phe (c.217G>T) pathogenic?

CDCA5 p.Val73Phe (c.217G>T) is classified Uncertain significance in CDCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1134); Rare (popmax 0.139%, sas).

How common is CDCA5 p.Val73Phe (c.217G>T) in the general population?

CDCA5 p.Val73Phe (c.217G>T) is rare (popmax 0.139%, sas) (gnomAD).

What do computational predictors say about CDCA5 p.Val73Phe (c.217G>T)?

AlphaMissense predicts likely benign (score 0.1134) — an in-silico prediction, not a clinical call.

CDCA5 p.Val73Phe

c.217G>T · rs757998694 · VCV2388887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1134 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1134	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -7.54	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 -0.16	GERP 0.11
Regional constraint	o/e 0.95	unconstrained · MANE · 4,868 bp · p 0.33 · regional, not allelic
Overall
CADD	16.33	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 0.139% South Asian · 127/91,088 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.00892% 144/1,614,212 alleles · rare exomes 137/1,461,890 · genomes 7/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.139%	717
Remaining individualsnot grpmax-eligible	0.0256%	3,907
European (non-Finnish)	8.47e-05%	1,180,048

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.Val73Phe
Coding: c.217G>T
MANE Select: NM_080668
dbSNP: rs757998694
Type: single nucleotide variant
Location: chr11:65083390 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.04
Residue 73: the 'disordered' region

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-val73phe (accessed [today's date]).

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