Is CEP104 p.Arg638= (c.1914A>G) pathogenic?

CEP104 p.Arg638= (c.1914A>G) is classified Benign in CEP104 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 12.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 25.

What condition is associated with CEP104 p.Arg638= (c.1914A>G)?

CEP104 p.Arg638= (c.1914A>G) is associated with Joubert syndrome 25 (ClinVar).

CEP104 p.Arg638=

Q: How common is CEP104 p.Arg638= (c.1914A>G) in the general population?

CEP104 p.Arg638= (c.1914A>G) is common (popmax 12.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1914A>G · rs2275829 · VCV475460

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 12.3%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Joubert syndrome 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4
Overall
CADD	3.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.3% East Asian · 5,505/44,876 alleles

Filtering AF 12% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.9%

Overall 0.454% 7,322/1,614,168 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	12.3%	8
Finnishnot grpmax-eligible	1.54%	65
Remaining individualsnot grpmax-eligible	0.379%	264
South Asian	0.194%	515
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
European (non-Finnish)	0.032%	3,122
Admixed American	0.0217%	4,617
African / African-American	0.00533%	18,762

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: CEP104
Protein: p.Arg638=
Coding: c.1914A>G
MANE Select: NM_014704
dbSNP: rs2275829
Type: single nucleotide variant
Location: chr1:3829920 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 638: a UniProt-annotated variant site (in mrt77); an α-helix

Full CEP104 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP104 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Arg55Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Glu627Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Lys270Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Tyr253Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 c.1120-5T>A Uncertain significance ★★ same condition
CEP104 p.Ala269Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala28Val 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/cep104-p-arg638 (accessed [today's date]).

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