Is CDCA2 p.Gly184Cys (c.550G>T) pathogenic?

CDCA2 p.Gly184Cys (c.550G>T) is classified Uncertain significance in CDCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: likely benign (0.133); Very rare (popmax 0.00542%, afr).

How common is CDCA2 p.Gly184Cys (c.550G>T) in the general population?

CDCA2 p.Gly184Cys (c.550G>T) is very rare (popmax 0.00542%, afr) (gnomAD).

What do computational predictors say about CDCA2 p.Gly184Cys (c.550G>T)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

CDCA2 p.Gly184Cys

c.550G>T · rs199899316 · VCV3141002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00542%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.57	GERP -5.3, phastCons 0.005
Regional constraint	o/e 1.04	unconstrained · MANE · 47 kb · p 0.15 · regional, not allelic
Overall
CADD	18.99	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 0.00542% African / African-American · 4/73,852 alleles

Filtering AF 0.0038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00342%

Overall 0.0254% 402/1,582,794 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.07%	94
Remaining individualsnot grpmax-eligible	0.0673%	1,486
African / African-Americangrpmax	0.00542%	18,463
European (non-Finnish)	0.00482%	20,767

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gly184Cys
Coding: c.550G>T
MANE Select: NM_152562
dbSNP: rs199899316
Type: single nucleotide variant
Location: chr8:25468228 (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-gly184cys (accessed [today's date]).

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