Is CDC45 p.Val106= (c.318C>T) pathogenic?

CDC45 p.Val106= (c.318C>T) is classified Uncertain significance in CDC45 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-31). Ultra-rare (popmax 0.0134%, eas); Associated with Meier-Gorlin syndrome 7.

What condition is associated with CDC45 p.Val106= (c.318C>T)?

CDC45 p.Val106= (c.318C>T) is associated with Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.Val106= (c.318C>T) in the general population?

CDC45 p.Val106= (c.318C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

CDC45 p.Val106=

c.318C>T · rs745800041 · VCV253098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Meier-Gorlin syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Pangolin	Δ0.31	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6.1	GERP -3.3
Overall
CADD	0.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,888 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.0013% 21/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
Admixed American	0.00333%	30,012
Remaining individualsnot grpmax-eligible	0.0032%	31,248
European (non-Finnish)	0.000932%	107,260

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: CDC45
Protein: p.Val106=
Coding: c.318C>T
MANE Select: NM_003504
dbSNP: rs745800041
Type: single nucleotide variant
Location: chr22:19482803 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 106: an α-helix

Full CDC45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meier-Gorlin syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDC45 p.Ile509Val Uncertain significance ★★ ⚠ same condition
CDC45 p.Pro496Leu Uncertain significance ★★ ⚠ same condition
CDC45 p.Ala298Val Likely pathogenic ★ ⚠ same condition
CDC45 p.Asn76His Likely pathogenic ★ same condition
CDC45 p.Asp226Gly Likely pathogenic ★ ⚠ same condition
CDC45 p.Gln68Arg Likely pathogenic ★ ⚠ same condition
CDC45 p.Glu548Ter Pathogenic ★ same condition

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/cdc45-p-val106 (accessed [today's date]).

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