Is CDCA2 p.Arg328His (c.983G>A) pathogenic?

CDCA2 p.Arg328His (c.983G>A) is classified Uncertain significance in CDCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: ambiguous (0.3435); Ultra-rare (popmax 0.0274%, nfe).

How common is CDCA2 p.Arg328His (c.983G>A) in the general population?

CDCA2 p.Arg328His (c.983G>A) is ultra-rare (popmax 0.0274%, nfe) (gnomAD).

What do computational predictors say about CDCA2 p.Arg328His (c.983G>A)?

AlphaMissense predicts ambiguous (score 0.3435) — an in-silico prediction, not a clinical call.

CDCA2 p.Arg328His

c.983G>A · rs142322892 · VCV2346394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3435 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3435	ambiguous
REVEL	0.356	indeterminate
SaProt	LLR -8.59	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 47 kb · p 0.15 · regional, not allelic
Overall
CADD	24.7	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 0.0274% European (non-Finnish) · 323/1,180,036 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.0215% 347/1,613,990 alleles · ultra-rare exomes 326/1,461,870 · genomes 21/152,120 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0274%	3,653
Remaining individualsnot grpmax-eligible	0.0272%	3,676
East Asian	0.00446%	22,441
African / African-American	0.00401%	24,968
South Asian	0.0022%	45,541

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: CDCA2
Protein: p.Arg328His
Coding: c.983G>A
MANE Select: NM_152562
dbSNP: rs142322892
Type: single nucleotide variant
Location: chr8:25480075 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.61 · 4 PDB

Full CDCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDCA2 p.Val467Ile Uncertain significance ★★ ⚠ same type
CDCA2 p.Lys754Thr Benign ★★ same type
CDCA2 p.Ser291= Benign ★★ same type
CDCA2 p.Thr50Ile Benign ★★ same type
CDCA2 p.Ala187Thr Uncertain significance ★ ⚠ same type
CDCA2 p.Ala217Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala23Val Uncertain significance ★ ⚠ same type
CDCA2 p.Ala92Gly 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/cdca2-p-arg328his (accessed [today's date]).

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