Is CDCA8 p.Glu40Gln (c.118G>C) pathogenic?

CDCA8 p.Glu40Gln (c.118G>C) is classified Likely benign in CDCA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.0824); Very rare (popmax 8.47e-05%, nfe).

How common is CDCA8 p.Glu40Gln (c.118G>C) in the general population?

CDCA8 p.Glu40Gln (c.118G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDCA8 p.Glu40Gln (c.118G>C)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

CDCA8 p.Glu40Gln

c.118G>C · rs2523063562 · VCV2308015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -8.02	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 4.5	GERP -0.2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 0.00025 · regional, not allelic
Overall
CADD	17.46	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,852 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: CDCA8
Protein: p.Glu40Gln
Coding: c.118G>C
MANE Select: NM_001256875
dbSNP: rs2523063562
Type: single nucleotide variant
Location: chr1:37692928 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.28 · 15 PDB
Residue 40: the 'required for interaction with senp3' region; the 'required for centromere localization' region; the 'required for interaction with incenp' region; the 'required to form a minimal cpc core complex that localizes to the central spindle and midbody and properly executes the role of the cpc during cytokinesis' region; an α-helix; the 'required for interaction with incenp and birc5' region

Full CDCA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA8 p.Ala140Val Uncertain significance ★ ⚠ same type
CDCA8 p.Ala173Val Uncertain significance ★ ⚠ same type
CDCA8 p.Arg166Cys Uncertain significance ★ ⚠ same type
CDCA8 p.Arg176Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg210Trp Uncertain significance ★ ⚠ same type
CDCA8 p.Arg240Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg277Gln Uncertain significance ★ ⚠ same type
CDCA8 p.Arg35Gln 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/cdca8-p-glu40gln (accessed [today's date]).

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