Is CDCA7 p.Pro395Leu (c.1184C>T) pathogenic?

CDCA7 p.Pro395Leu (c.1184C>T) is classified Uncertain significance in CDCA7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.3576); Ultra-rare (popmax 0.03%, amr).

How common is CDCA7 p.Pro395Leu (c.1184C>T) in the general population?

CDCA7 p.Pro395Leu (c.1184C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about CDCA7 p.Pro395Leu (c.1184C>T)?

AlphaMissense predicts ambiguous (score 0.3576) — an in-silico prediction, not a clinical call.

CDCA7 p.Pro395Leu

c.1184C>T · rs143579439 · VCV1422380

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Computational evidence

Protein change
AlphaMissense	0.3576	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -11.43	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 1,346 bp · p 0.00038 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P316L vs ClinVar P395L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,972 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0031% 50/1,613,838 alleles · ultra-rare exomes 47/1,461,594 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,332
South Asian	0.00879%	11,382
European (non-Finnish)	0.00186%	53,630
Remaining individualsnot grpmax-eligible	0.0016%	62,492
African / African-American	0.00133%	75,000

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.Pro395Leu
Coding: c.1184C>T
MANE Select: NM_031942
dbSNP: rs143579439
Type: single nucleotide variant
Location: chr2:173366431 (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.Pro395= Uncertain significance ★ same residue
CDCA7 c.384+2T>C Uncertain significance ★★ same type
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

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-pro395leu (accessed [today's date]).

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