Is CEP250 p.Arg490Ter (c.1468C>T) pathogenic?

CEP250 p.Arg490Ter (c.1468C>T) is classified Pathogenic in CEP250 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Very rare (popmax 0.00535%, afr).

How common is CEP250 p.Arg490Ter (c.1468C>T) in the general population?

CEP250 p.Arg490Ter (c.1468C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

CEP250 p.Arg490Ter

c.1468C>T · rs776554898 · VCV1452407

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,704 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000931% 15/1,611,574 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,676
East Asian	0.00223%	44,760
Admixed American	0.00169%	59,228
Finnishnot grpmax-eligible	0.00156%	63,984
South Asian	0.0011%	90,768
European (non-Finnish)	0.000594%	168,470

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: CEP250
Protein: p.Arg490Ter
Coding: c.1468C>T
MANE Select: NM_007186
dbSNP: rs776554898
Type: single nucleotide variant
Location: chr20:35473949 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 490: a UniProt-annotated variant site (in crdhl2); a UniProt-annotated variant site (in crdhl2; also found in a family with non-syndromic retinitis pigmentosa)

Full CEP250 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP250 p.Arg490Gln Uncertain significance ★★ ⚠ same residue
CEP250 p.Arg490= Likely benign ★ same residue
CEP250 p.Arg1045Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1155Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1336Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1343Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same type
CEP250 p.Arg1695Ter Pathogenic/Likely pathogenic ★★ 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/cep250-p-arg490ter (accessed [today's date]).

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