Is CDC7 p.Pro372Ala (c.1114C>G) pathogenic?

CDC7 p.Pro372Ala (c.1114C>G) is classified Uncertain significance in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: ambiguous (0.5198); Ultra-rare (popmax 0.0427%, afr).

How common is CDC7 p.Pro372Ala (c.1114C>G) in the general population?

CDC7 p.Pro372Ala (c.1114C>G) is ultra-rare (popmax 0.0427%, afr) (gnomAD).

What do computational predictors say about CDC7 p.Pro372Ala (c.1114C>G)?

AlphaMissense predicts ambiguous (score 0.5198) — an in-silico prediction, not a clinical call.

CDC7 p.Pro372Ala

c.1114C>G · rs367577234 · VCV3140979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, afr)

Computational evidence

Protein change
AlphaMissense	0.5198	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -5.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.96, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	27.4	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 0.0427% African / African-American · 32/75,004 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00217% 35/1,613,700 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0427%	2,344
Admixed American	0.00333%	29,992
European (non-Finnish)	8.48e-05%	1,179,796

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.Pro372Ala
Coding: c.1114C>G
MANE Select: NM_003503
dbSNP: rs367577234
Type: single nucleotide variant
Location: chr1:91515810 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 372: the protein kinase domain

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-pro372ala (accessed [today's date]).

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