Is CDC45 p.Gln68Arg (c.203A>G) pathogenic?

CDC45 p.Gln68Arg (c.203A>G) is classified Likely pathogenic in CDC45 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-10-15). AlphaMissense: likely benign (0.2153); Very rare (popmax 8.55e-05%, nfe); Associated with Meier-Gorlin syndrome 7.

What condition is associated with CDC45 p.Gln68Arg (c.203A>G)?

CDC45 p.Gln68Arg (c.203A>G) is associated with Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.Gln68Arg (c.203A>G) in the general population?

CDC45 p.Gln68Arg (c.203A>G) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about CDC45 p.Gln68Arg (c.203A>G)?

AlphaMissense predicts likely benign (score 0.2153) — an in-silico prediction, not a clinical call.

CDC45 p.Gln68Arg

c.203A>G · rs879255633 · VCV253102

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Meier-Gorlin syndrome 7

Computational evidence

Protein change
AlphaMissense	0.2153	likely benign ⚠ discordant with ClinVar
REVEL	0.447	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.77	donor loss · deltas
Pangolin	Δ0.72	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	32.0	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 8.55e-05% European (non-Finnish) · 1/1,169,482 alleles

Overall 6.9e-05% 1/1,448,460 alleles · very rare

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.Gln68Arg
Coding: c.203A>G
MANE Select: NM_003504
dbSNP: rs879255633
Type: single nucleotide variant
Location: chr22:19481044 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 68: a turn; a UniProt-annotated variant site (in mgors7; decreased protein level)

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.Gln68= Likely pathogenic same residue
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.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-gln68arg (accessed [today's date]).

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