Is CDCA7 p.Ser183Pro (c.547T>C) pathogenic?

CDCA7 p.Ser183Pro (c.547T>C) is classified Uncertain significance in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.1361); Very rare (popmax 0.00119%, nfe); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Ser183Pro (c.547T>C)?

CDCA7 p.Ser183Pro (c.547T>C) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

How common is CDCA7 p.Ser183Pro (c.547T>C) in the general population?

CDCA7 p.Ser183Pro (c.547T>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CDCA7 p.Ser183Pro (c.547T>C)?

AlphaMissense predicts likely benign (score 0.1361) — an in-silico prediction, not a clinical call.

CDCA7 p.Ser183Pro

c.547T>C · rs1333528726 · VCV2921138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 3

Computational evidence

Protein change
AlphaMissense	0.1361	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.25, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 11 kb · p 0.02 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S104P vs ClinVar S183P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,024 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,892 alleles · very rare

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.Ser183Pro
Coding: c.547T>C
MANE Select: NM_031942
dbSNP: rs1333528726
Type: single nucleotide variant
Location: chr2:173363388 (GRCh38)
Gene constraint: LOEUF 0.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.93 · 2 PDB
Residue 183: the 'disordered' region

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.Ser183= Likely benign ★★ 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-ser183pro (accessed [today's date]).

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