Is CEP250 p.Arg950Ter (c.2848C>T) pathogenic?

CEP250 p.Arg950Ter (c.2848C>T) is classified Pathogenic in CEP250 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-02-13). Very rare (popmax 0.00225%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CEP250 p.Arg950Ter (c.2848C>T)?

CEP250 p.Arg950Ter (c.2848C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CEP250 p.Arg950Ter (c.2848C>T) in the general population?

CEP250 p.Arg950Ter (c.2848C>T) is very rare (popmax 0.00225%, eas) (gnomAD).

CEP250 p.Arg950Ter

c.2848C>T · rs1388902455 · VCV1458267

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

Conditions

inherited retinal dystrophy

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 22 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 2.2, phastCons 0.98
Overall
CADD	44.0	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 0.00225% East Asian · 1/44,374 alleles

Overall 0.000138% 2/1,450,106 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00225%	44,374
European (non-Finnish)	8.52e-05%	1,173,942

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.Arg950Ter
Coding: c.2848C>T
MANE Select: NM_007186
dbSNP: rs1388902455
Type: single nucleotide variant
Location: chr20:35491305 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 950: 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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP250 p.Arg950Gln Uncertain significance ★ ⚠ same residue
CEP250 p.Ala1988Val Uncertain significance ★★ ⚠ same condition
CEP250 p.Arg1992His Uncertain significance ★★ ⚠ same condition
CEP250 p.Arg519Trp Uncertain significance ★★ ⚠ same condition
CEP250 p.Arg632Gly Uncertain significance ★★ ⚠ same condition
CEP250 p.Leu2178Phe Uncertain significance ★★ ⚠ same condition
CEP250 p.Ala2440Thr Uncertain significance ★ ⚠ same condition
CEP250 p.Ala609Val Conflicting classifications of pathogenicity ★ ⚠ 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/cep250-p-arg950ter (accessed [today's date]).

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