Is CDCA7 p.Arg249= (c.745A>C) pathogenic?

CDCA7 p.Arg249= (c.745A>C) is classified Conflicting classifications of pathogenicity in CDCA7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.144%, nfe); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Arg249= (c.745A>C)?

CDCA7 p.Arg249= (c.745A>C) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

How common is CDCA7 p.Arg249= (c.745A>C) in the general population?

CDCA7 p.Arg249= (c.745A>C) is rare (popmax 0.144%, nfe) (gnomAD).

CDCA7 p.Arg249=

c.745A>C · rs146148251 · VCV707884

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.144%, nfe)

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.4	GERP 0.38, phastCons 0.68
Overall
CADD	12.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.144% European (non-Finnish) · 1,699/1,179,156 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.108% 1,741/1,611,396 alleles · rare exomes 1,664/1,459,046 · genomes 77/152,350 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.144%	694
Remaining individualsnot grpmax-eligible	0.0481%	2,080
African / African-American	0.0134%	7,482
Finnishnot grpmax-eligible	0.00312%	32,014

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: CDCA7
Protein: p.Arg249=
Coding: c.745A>C
MANE Select: NM_031942
dbSNP: rs146148251
Type: single nucleotide variant
Location: chr2:173364840 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 249: an α-helix

Full CDCA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency-centromeric instability-facial anomalies syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDCA7 p.Ala391Gly Uncertain significance ★★ ⚠ same condition
CDCA7 p.Pro244Leu Uncertain significance ★★ ⚠ same condition
CDCA7 c.22-17G>T Benign ★★ same condition
CDCA7 c.622-128C>T Benign ★★ same condition
CDCA7 c.895-27C>G Benign ★★ same condition
CDCA7 p.Asn331= Likely benign ★★ same condition
CDCA7 p.Thr359= Benign ★★ same condition
CDCA7 p.Arg353Cys Likely pathogenic ★ same condition

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/cdca7-p-arg249 (accessed [today's date]).

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