Is CDCA7 p.Arg353Cys (c.1057C>T) pathogenic?

CDCA7 p.Arg353Cys (c.1057C>T) is classified Likely pathogenic in CDCA7 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.9947); Very rare (popmax 0.00223%, eas); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Arg353Cys (c.1057C>T)?

CDCA7 p.Arg353Cys (c.1057C>T) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

How common is CDCA7 p.Arg353Cys (c.1057C>T) in the general population?

CDCA7 p.Arg353Cys (c.1057C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDCA7 p.Arg353Cys (c.1057C>T)?

AlphaMissense predicts likely pathogenic (score 0.9947) — an in-silico prediction, not a clinical call.

CDCA7 p.Arg353Cys

c.1057C>T · rs879253738 · VCV225529

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 3

Computational evidence

Protein change
AlphaMissense	0.9947	likely pathogenic ✓ concordant with ClinVar · top 8% in CDCA7
REVEL	0.619	indeterminate
SaProt	LLR -14.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 727 bp · p 0.00096 · regional, not allelic
Overall
CADD	32.0	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 R274C vs ClinVar R353C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,461,594 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
European (non-Finnish)	0.000424%	235,975

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.Arg353Cys
Coding: c.1057C>T
MANE Select: NM_031942
dbSNP: rs879253738
Type: single nucleotide variant
Location: chr2:173366304 (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

Disease context

immunodeficiency-centromeric instability-facial anomalies syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDCA7 p.Arg353His Likely pathogenic ★ 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.Asn331= Likely benign ★★ same condition
CDCA7 p.Thr359= Benign ★★ 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-arg353cys (accessed [today's date]).

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