Is CDC7 p.Arg188Cys (c.562C>T) pathogenic?

CDC7 p.Arg188Cys (c.562C>T) is classified Uncertain significance in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00906%, eas).

How common is CDC7 p.Arg188Cys (c.562C>T) in the general population?

CDC7 p.Arg188Cys (c.562C>T) is very rare (popmax 0.00906%, eas) (gnomAD).

What do computational predictors say about CDC7 p.Arg188Cys (c.562C>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

CDC7 p.Arg188Cys

c.562C>T · rs539320135 · VCV3140985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00906%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -10.50	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.96, phastCons 0.55
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00906% East Asian · 4/44,148 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00257%

Overall 0.00349% 55/1,573,832 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00906%	11,037
European (non-Finnish)	0.00381%	26,228
South Asian	0.00354%	28,233
Remaining individualsnot grpmax-eligible	0.00329%	30,377
African / African-American	0.00271%	36,911

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: CDC7
Protein: p.Arg188Cys
Coding: c.562C>T
MANE Select: NM_003503
dbSNP: rs539320135
Type: single nucleotide variant
Location: chr1:91511913 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 188: the protein kinase domain; a turn

Full CDC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC7 p.Arg188His Uncertain significance ★ ⚠ same residue
CDC7 c.-124A>G Benign ★★ same type
CDC7 p.Ala254Gly Uncertain significance ★ ⚠ same type
CDC7 p.Ala254Ser Uncertain significance ★ ⚠ same type
CDC7 p.Ala355Val Uncertain significance ★ ⚠ same type
CDC7 p.Ala38Glu Uncertain significance ★ ⚠ same type
CDC7 p.Ala38Thr Uncertain significance ★ ⚠ same type
CDC7 p.Ala50Val 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/cdc7-p-arg188cys (accessed [today's date]).

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