Is CDCA2 p.Thr50Ile (c.149C>T) pathogenic?

CDCA2 p.Thr50Ile (c.149C>T) is classified Benign in CDCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-25). AlphaMissense: likely benign (0.1032); Common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CDCA2 p.Thr50Ile (c.149C>T)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

CDCA2 p.Thr50Ile

Q: How common is CDCA2 p.Thr50Ile (c.149C>T) in the general population?

CDCA2 p.Thr50Ile (c.149C>T) is common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.149C>T · rs115875864 · VCV785245

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.26	GERP -0.23
Regional constraint	o/e 1.04	unconstrained · MANE · 47 kb · p 0.15 · regional, not allelic
Overall
CADD	15.48	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 6.53% African / African-American · 4,904/75,048 alleles

Filtering AF 6.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.32%

Overall 0.346% 5,587/1,614,174 alleles · common exomes 2,754/1,461,860 · genomes 2,833/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.53%	15
Admixed American	0.445%	225
Remaining individualsnot grpmax-eligible	0.429%	233
Middle Eastern	0.231%	433
South Asian	0.0154%	6,506
European (non-Finnish)	0.0102%	9,834

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.Thr50Ile
Coding: c.149C>T
MANE Select: NM_152562
dbSNP: rs115875864
Type: single nucleotide variant
Location: chr8:25460471 (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.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
CDCA2 p.Arg106His 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-thr50ile (accessed [today's date]).

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