Is CDCA7 c.384+2T>C pathogenic?

CDCA7 c.384+2T>C is classified Uncertain significance in CDCA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-17). Very rare (popmax 0.0066%, sas).

How common is CDCA7 c.384+2T>C in the general population?

CDCA7 c.384+2T>C is very rare (popmax 0.0066%, sas) (gnomAD).

CDCA7 c.384+2T>C

rs1029449817 · VCV2183723

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0066%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.89	loss · gain 0.79 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Non-coding constraint	Z -0.01	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	34.0	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 0.0066% South Asian · 6/90,962 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000683% 11/1,610,482 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0066%	15,160
Remaining individualsnot grpmax-eligible	0.0016%	62,374
European (non-Finnish)	0.00034%	294,215

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
Coding: c.384+2T>C
MANE Select: NM_031942
dbSNP: rs1029449817
Type: single nucleotide variant
Location: chr2:173359493 (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.Ala157Val Uncertain significance ★★ ⚠ same type
CDCA7 p.Ala391Gly Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg134Leu Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg134Trp Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg171Cys Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg171Leu Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg239Gln Uncertain significance ★★ ⚠ same type
CDCA7 p.Arg254Leu 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-c-384-plus-2t-c (accessed [today's date]).

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