Is CDC7 p.Arg187Lys (c.560G>A) pathogenic?

CDC7 p.Arg187Lys (c.560G>A) is classified Uncertain significance in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.2767); Ultra-rare (popmax 0.0527%, afr).

How common is CDC7 p.Arg187Lys (c.560G>A) in the general population?

CDC7 p.Arg187Lys (c.560G>A) is ultra-rare (popmax 0.0527%, afr) (gnomAD).

What do computational predictors say about CDC7 p.Arg187Lys (c.560G>A)?

AlphaMissense predicts likely benign (score 0.2767) — an in-silico prediction, not a clinical call.

CDC7 p.Arg187Lys

c.560G>A · rs747270363 · VCV3140984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2767	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -11.45	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	25.7	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 0.0527% African / African-American · 39/73,982 alleles

Filtering AF 0.0396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.00253% 40/1,579,178 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0527%	1,897
Remaining individualsnot grpmax-eligible	0.00164%	60,992

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.Arg187Lys
Coding: c.560G>A
MANE Select: NM_003503
dbSNP: rs747270363
Type: single nucleotide variant
Location: chr1:91511911 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 187: the protein kinase domain; a turn

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

Similar variants

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
CDC7 p.Arg167His 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-arg187lys (accessed [today's date]).

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