Is CDC45 p.Ser264Tyr (c.791C>A) pathogenic?

CDC45 p.Ser264Tyr (c.791C>A) is classified Uncertain significance in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-15). AlphaMissense: ambiguous (0.4098); Very rare (popmax 0.000508%, nfe); Associated with Meier-Gorlin syndrome 7.

What condition is associated with CDC45 p.Ser264Tyr (c.791C>A)?

CDC45 p.Ser264Tyr (c.791C>A) is associated with Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.Ser264Tyr (c.791C>A) in the general population?

CDC45 p.Ser264Tyr (c.791C>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CDC45 p.Ser264Tyr (c.791C>A)?

AlphaMissense predicts ambiguous (score 0.4098) — an in-silico prediction, not a clinical call.

CDC45 p.Ser264Tyr

c.791C>A · rs151279621 · VCV617920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

Meier-Gorlin syndrome 7

Computational evidence

Protein change
AlphaMissense	0.4098	ambiguous
REVEL	0.472	indeterminate
SaProt	LLR -3.07	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	24.1	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 0.000508% European (non-Finnish) · 6/1,179,992 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,044 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.Ser264Tyr
Coding: c.791C>A
MANE Select: NM_003504
dbSNP: rs151279621
Type: single nucleotide variant
Location: chr22:19505448 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 264: a UniProt-annotated variant site (in mgors7; uncertain significance)

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.Ser264= Likely benign ★★ 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.Gln68Arg Likely 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-ser264tyr (accessed [today's date]).

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