Is CDCA7 p.Thr359= (c.1077C>G) pathogenic?

CDCA7 p.Thr359= (c.1077C>G) is classified Benign in CDCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Thr359= (c.1077C>G)?

CDCA7 p.Thr359= (c.1077C>G) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

CDCA7 p.Thr359=

Q: How common is CDCA7 p.Thr359= (c.1077C>G) in the general population?

CDCA7 p.Thr359= (c.1077C>G) is common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1077C>G · rs116079323 · VCV785981

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.04%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.83, phastCons 1
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.04% African / African-American · 4,525/74,914 alleles

Filtering AF 5.89% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.83%

Overall 0.331% 5,347/1,613,902 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.04%	17
Middle Eastern	0.511%	196
Remaining individualsnot grpmax-eligible	0.445%	225
Admixed American	0.435%	230
European (non-Finnish)	0.0203%	4,937
South Asian	0.0143%	7,005

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.Thr359=
Coding: c.1077C>G
MANE Select: NM_031942
dbSNP: rs116079323
Type: single nucleotide variant
Location: chr2:173366324 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 359: 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.Arg353Cys Likely pathogenic ★ same condition
CDCA7 p.Arg353His 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-thr359 (accessed [today's date]).

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