Is CEP63 p.Arg548Ser (c.1644A>T) pathogenic?

CEP63 p.Arg548Ser (c.1644A>T) is classified Uncertain significance in CEP63 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.1974); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEP63 p.Arg548Ser (c.1644A>T)?

CEP63 p.Arg548Ser (c.1644A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP63 p.Arg548Ser (c.1644A>T) in the general population?

CEP63 p.Arg548Ser (c.1644A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP63 p.Arg548Ser (c.1644A>T)?

AlphaMissense predicts likely benign (score 0.1974) — an in-silico prediction, not a clinical call.

CEP63 p.Arg548Ser

c.1644A>T · VCV3490871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1974	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.68	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 4.4	GERP 0.69, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 66 kb · p 0.39 · regional, not allelic
Overall
CADD	21.1	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: CEP63
Protein: p.Arg548Ser
Coding: c.1644A>T
MANE Select: NM_001353108
Type: single nucleotide variant
Location: chr3:134558318 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.95 · 4 PDB

Full CEP63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP63 p.Arg215Trp Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg46His Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg474His Uncertain significance ★★ ⚠ same condition
CEP63 p.Arg57His Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn301Ile Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn633Asp Uncertain significance ★★ ⚠ same condition
CEP63 p.Asn633Ser Uncertain significance ★★ ⚠ same condition
CEP63 p.Gln645Glu Uncertain significance ★★ ⚠ 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/cep63-p-arg548ser (accessed [today's date]).

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