Is CDCA8 p.Arg35Gln (c.104G>A) pathogenic?

CDCA8 p.Arg35Gln (c.104G>A) is classified Uncertain significance in CDCA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.2881); Ultra-rare (popmax 0.012%, afr).

How common is CDCA8 p.Arg35Gln (c.104G>A) in the general population?

CDCA8 p.Arg35Gln (c.104G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CDCA8 p.Arg35Gln (c.104G>A)?

AlphaMissense predicts likely benign (score 0.2881) — an in-silico prediction, not a clinical call.

CDCA8 p.Arg35Gln

c.104G>A · VCV3265094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2881	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -11.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 16 kb · p 0.00025 · regional, not allelic
Overall
CADD	27.8	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 0.012% African / African-American · 9/74,894 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000744% 12/1,613,924 alleles · ultra-rare exomes 4/1,461,818 · genomes 8/152,106 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,322
Admixed American	0.005%	19,998

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.Arg35Gln
Coding: c.104G>A
MANE Select: NM_001256875
Type: single nucleotide variant
Location: chr1:37692914 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.28 · 15 PDB
Residue 35: 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.Asp120Glu 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-arg35gln (accessed [today's date]).

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