Is CDCA7 p.Asp112Ter (c.333dup) pathogenic?

CDCA7 p.Asp112Ter (c.333dup) is classified Uncertain significance in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-07). Very rare (popmax 0.00167%, amr).

How common is CDCA7 p.Asp112Ter (c.333dup) in the general population?

CDCA7 p.Asp112Ter (c.333dup) is very rare (popmax 0.00167%, amr) (gnomAD).

CDCA7 p.Asp112Ter

c.333dup · rs773668313 · VCV1424108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2.6, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
European (non-Finnish)	0.000339%	295,012

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.Asp112Ter
Coding: c.333dup
MANE Select: NM_031942
dbSNP: rs773668313
Type: Duplication
Location: chr2:173359439 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB

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

Similar variants

CDCA7 p.Asp112= Likely benign ★ same residue
CDCA7 p.Tyr66fs Uncertain significance ★★ same type
CDCA7 c.1322+19dup Benign/Likely benign ★★ same type
CDCA7 p.Tyr341fs 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/cdca7-p-asp112ter (accessed [today's date]).

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