Is CDC7 p.Ile44Ser (c.131T>G) pathogenic?

CDC7 p.Ile44Ser (c.131T>G) is classified Uncertain significance in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.6225); Absent from gnomAD v4.1.

How common is CDC7 p.Ile44Ser (c.131T>G) in the general population?

CDC7 p.Ile44Ser (c.131T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC7 p.Ile44Ser (c.131T>G)?

AlphaMissense predicts likely pathogenic (score 0.6225) — an in-silico prediction, not a clinical call.

CDC7 p.Ile44Ser

c.131T>G · VCV4223455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6225 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6225	likely pathogenic
REVEL	0.392	indeterminate
SaProt	LLR -14.06	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDC7
Protein: p.Ile44Ser
Coding: c.131T>G
MANE Select: NM_003503
Type: single nucleotide variant
Location: chr1:91507869 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 44: an α-helix

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-ile44ser (accessed [today's date]).

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