Is CDCA7 p.Asn331= (c.993C>T) pathogenic?

CDCA7 p.Asn331= (c.993C>T) is classified Likely benign in CDCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0275%, nfe); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Asn331= (c.993C>T)?

CDCA7 p.Asn331= (c.993C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

How common is CDCA7 p.Asn331= (c.993C>T) in the general population?

CDCA7 p.Asn331= (c.993C>T) is ultra-rare (popmax 0.0275%, nfe) (gnomAD).

CDCA7 p.Asn331=

c.993C>T · rs762377778 · VCV1672916

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, nfe)

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 0.11	GERP -0.42, phastCons 0.93
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% European (non-Finnish) · 325/1,180,026 alleles

Filtering AF 0.025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.0214% 346/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0275%	3,631
African / African-American	0.0147%	6,811
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00333%	29,991
South Asian	0.00329%	30,360

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.Asn331=
Coding: c.993C>T
MANE Select: NM_031942
dbSNP: rs762377778
Type: single nucleotide variant
Location: chr2:173365550 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 331: a turn

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.Asn331Lys Uncertain significance ★ ⚠ same residue
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.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-asn331 (accessed [today's date]).

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