Is CDCA7 p.Arg319Cys (c.955C>T) pathogenic?

CDCA7 p.Arg319Cys (c.955C>T) is classified Uncertain significance in CDCA7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.4146); Ultra-rare (popmax 0.065%, amr).

How common is CDCA7 p.Arg319Cys (c.955C>T) in the general population?

CDCA7 p.Arg319Cys (c.955C>T) is ultra-rare (popmax 0.065%, amr) (gnomAD).

What do computational predictors say about CDCA7 p.Arg319Cys (c.955C>T)?

AlphaMissense predicts ambiguous (score 0.4146) — an in-silico prediction, not a clinical call.

CDCA7 p.Arg319Cys

c.955C>T · rs775525324 · VCV1345758

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, amr)

Computational evidence

Protein change
AlphaMissense	0.4146	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -13.55	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	33.0	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 R240C vs ClinVar R319C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.065% Admixed American · 39/59,998 alleles

Filtering AF 0.0488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.00279% 45/1,614,024 alleles · ultra-rare exomes 20/1,461,874 · genomes 25/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.065%	1,538
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.000424%	236,005

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.Arg319Cys
Coding: c.955C>T
MANE Select: NM_031942
dbSNP: rs775525324
Type: single nucleotide variant
Location: chr2:173365512 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 240 UniProt numbering: an α-helix

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

Similar variants

CDCA7 p.Arg319= Likely benign ★ 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-arg319cys (accessed [today's date]).

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