Is CDK5RAP3 p.Ser248Pro (c.742T>C) pathogenic?

CDK5RAP3 p.Ser248Pro (c.742T>C) is classified Uncertain significance in CDK5RAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1939); Absent from gnomAD v4.1.

How common is CDK5RAP3 p.Ser248Pro (c.742T>C) in the general population?

CDK5RAP3 p.Ser248Pro (c.742T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK5RAP3 p.Ser248Pro (c.742T>C)?

AlphaMissense predicts likely benign (score 0.1939) — an in-silico prediction, not a clinical call.

CDK5RAP3 p.Ser248Pro

c.742T>C · rs2509331866 · VCV3141597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1939 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1939	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -9.82	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 -0.51	GERP 0.42
Regional constraint	o/e 0.95	unconstrained · MANE · 7,724 bp · p 0.32 · regional, not allelic
Overall
CADD	14.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CDK5RAP3
Protein: p.Ser248Pro
Coding: c.742T>C
MANE Select: NM_176096
dbSNP: rs2509331866
Type: single nucleotide variant
Location: chr17:47975957 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.29 · 5 PDB

Full CDK5RAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK5RAP3 p.Ser248Cys Uncertain significance ★ ⚠ same residue
CDK5RAP3 c.334+243G>A Uncertain significance ★ same type
CDK5RAP3 p.Ala196Val Uncertain significance ★ ⚠ same type
CDK5RAP3 p.Ala197Val Uncertain significance ★ ⚠ same type
CDK5RAP3 p.Ala266Val Uncertain significance ★ ⚠ same type
CDK5RAP3 p.Ala289Pro Uncertain significance ★ ⚠ same type
CDK5RAP3 p.Ala326Val Uncertain significance ★ ⚠ same type
CDK5RAP3 p.Ala466Val 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/cdk5rap3-p-ser248pro (accessed [today's date]).

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