Is CDCA4 p.Glu211Gly (c.632A>G) pathogenic?

CDCA4 p.Glu211Gly (c.632A>G) is classified Uncertain significance in CDCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1155); Very rare (popmax 0.000932%, nfe).

How common is CDCA4 p.Glu211Gly (c.632A>G) in the general population?

CDCA4 p.Glu211Gly (c.632A>G) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about CDCA4 p.Glu211Gly (c.632A>G)?

AlphaMissense predicts likely benign (score 0.1155) — an in-silico prediction, not a clinical call.

CDCA4 p.Glu211Gly

c.632A>G · rs1191070808 · VCV2302923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1155 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1155	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -5.97	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 4.7	GERP -0.23, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 722 bp · p 0.12 · regional, not allelic
Overall
CADD	21.2	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 0.000932% European (non-Finnish) · 11/1,179,980 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000753% 11/1,461,718 alleles · very rare

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.Glu211Gly
Coding: c.632A>G
MANE Select: NM_017955
dbSNP: rs1191070808
Type: single nucleotide variant
Location: chr14:105011298 (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.Glu211Lys Uncertain significance ★ ⚠ same residue
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

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-glu211gly (accessed [today's date]).

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