Is CDCA8 p.Glu95Asp (c.285A>C) pathogenic?

CDCA8 p.Glu95Asp (c.285A>C) is classified Uncertain significance in CDCA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: ambiguous (0.4801); Very rare (popmax 0.0011%, sas).

How common is CDCA8 p.Glu95Asp (c.285A>C) in the general population?

CDCA8 p.Glu95Asp (c.285A>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CDCA8 p.Glu95Asp (c.285A>C)?

AlphaMissense predicts ambiguous (score 0.4801) — an in-silico prediction, not a clinical call.

CDCA8 p.Glu95Asp

c.285A>C · rs774862393 · VCV2290320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.4801	ambiguous
REVEL	0.303	indeterminate
SaProt	LLR -6.23	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.41, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 0.00025 · regional, not allelic
Overall
CADD	23.2	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 0.0011% South Asian · 1/91,078 alleles

Overall 6.2e-05% 1/1,613,900 alleles · very rare exomes 1/1,461,558 · genomes 0/152,342 · joint denominator

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.Glu95Asp
Coding: c.285A>C
MANE Select: NM_001256875
dbSNP: rs774862393
Type: single nucleotide variant
Location: chr1:37698925 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.28 · 15 PDB
Residue 95: the 'required for interaction with senp3' 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

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-glu95asp (accessed [today's date]).

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