Is CDCA7 p.Arg383His (c.1148G>A) pathogenic?

CDCA7 p.Arg383His (c.1148G>A) is classified Conflicting classifications of pathogenicity in CDCA7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.9921); Very rare (popmax 0.00223%, eas); Associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3.

What condition is associated with CDCA7 p.Arg383His (c.1148G>A)?

CDCA7 p.Arg383His (c.1148G>A) is associated with immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ClinVar).

How common is CDCA7 p.Arg383His (c.1148G>A) in the general population?

CDCA7 p.Arg383His (c.1148G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDCA7 p.Arg383His (c.1148G>A)?

AlphaMissense predicts likely pathogenic (score 0.9921) — an in-silico prediction, not a clinical call.

CDCA7 p.Arg383His

c.1148G>A · rs772929976 · VCV225531

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency-centromeric instability-facial anomalies syndrome 3

Computational evidence

Protein change
AlphaMissense	0.9921	likely pathogenic · top 9% in CDCA7
REVEL	0.668	pathogenic-leaning
SaProt	LLR -13.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.85, 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 R304H vs ClinVar R383H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

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

Overall 0.00105% 17/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00119%	84,289
South Asian	0.0011%	91,090

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.Arg383His
Coding: c.1148G>A
MANE Select: NM_031942
dbSNP: rs772929976
Type: single nucleotide variant
Location: chr2:173366395 (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.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
CDCA7 p.Arg353Cys Likely pathogenic ★ 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-arg383his (accessed [today's date]).

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