Is CDCA7 p.Cys408Tyr (c.1223G>A) pathogenic?

CDCA7 p.Cys408Tyr (c.1223G>A) is classified Likely pathogenic in CDCA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.9982); Absent from gnomAD v4.1.

How common is CDCA7 p.Cys408Tyr (c.1223G>A) in the general population?

CDCA7 p.Cys408Tyr (c.1223G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDCA7 p.Cys408Tyr (c.1223G>A)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

CDCA7 p.Cys408Tyr

c.1223G>A · rs2468428826 · VCV1879493

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,066)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic ✓ concordant with ClinVar · top 4% in CDCA7
REVEL	0.721	pathogenic-leaning
SaProt	LLR -13.47	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 1,346 bp · p 0.00038 · 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 C329Y vs ClinVar C408Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,066). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDCA7
Protein: p.Cys408Tyr
Coding: c.1223G>A
MANE Select: NM_031942
dbSNP: rs2468428826
Type: single nucleotide variant
Location: chr2:173367187 (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 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
CDCA7 p.Arg239Gln 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-cys408tyr (accessed [today's date]).

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