Is CDC7 p.Ile208Met (c.624A>G) pathogenic?

CDC7 p.Ile208Met (c.624A>G) is classified Likely benign in CDC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely benign (0.1398); Rare (popmax 0.37%, nfe).

How common is CDC7 p.Ile208Met (c.624A>G) in the general population?

CDC7 p.Ile208Met (c.624A>G) is rare (popmax 0.37%, nfe) (gnomAD).

What do computational predictors say about CDC7 p.Ile208Met (c.624A>G)?

AlphaMissense predicts likely benign (score 0.1398) — an in-silico prediction, not a clinical call.

CDC7 p.Ile208Met

c.624A>G · rs34979509 · VCV2672339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1398 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.37%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1398	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.54, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.001 · regional, not allelic
Overall
CADD	23.3	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 0.37% European (non-Finnish) · 4,366/1,179,488 alleles

Filtering AF 0.361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.357%

Overall 0.316% 5,091/1,613,452 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
Finnishnot grpmax-eligible	0.415%	241
European (non-Finnish)grpmax	0.37%	270
Remaining individualsnot grpmax-eligible	0.272%	368
Admixed American	0.227%	441
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.0879%	1,138
South Asian	0.0758%	1,320
African / African-American	0.0587%	1,705

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile208Met
Coding: c.624A>G
MANE Select: NM_003503
dbSNP: rs34979509
Type: single nucleotide variant
Location: chr1:91513109 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 9 PDB
Residue 208: the protein kinase domain; a UniProt-annotated variant site (in)

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-ile208met (accessed [today's date]).

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