Is CEP250 p.Arg719Ter (c.2155C>T) pathogenic?

CEP250 p.Arg719Ter (c.2155C>T) is classified Pathogenic/Likely pathogenic in CEP250 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-04). Very rare (popmax 0.00333%, amr); Associated with CEP250-related disorder.

What condition is associated with CEP250 p.Arg719Ter (c.2155C>T)?

CEP250 p.Arg719Ter (c.2155C>T) is associated with CEP250-related disorder, cone-rod dystrophy and hearing loss 2 (ClinVar).

How common is CEP250 p.Arg719Ter (c.2155C>T) in the general population?

CEP250 p.Arg719Ter (c.2155C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

CEP250 p.Arg719Ter

c.2155C>T · rs1051944154 · VCV1459241

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

CEP250-related disorder

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 18 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.12, phastCons 0.88
Overall
CADD	36.0	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 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,896
European (non-Finnish)	0.000339%	295,009

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.Arg719Ter
Coding: c.2155C>T
MANE Select: NM_007186
dbSNP: rs1051944154
Type: single nucleotide variant
Location: chr20:35479291 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.68 · 1 PDB
Residue 719: 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

CEP250-related disorder

Also linked: cone-rod dystrophy and hearing loss 2

Similar variants

CEP250 p.Arg719Gln Uncertain significance ★ ⚠ same residue
CEP250 p.Arg1155Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg1336Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg1343Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg1695Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg1869Ter Pathogenic/Likely pathogenic ★★ same condition
CEP250 p.Arg188Ter Pathogenic ★★ 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-arg719ter (accessed [today's date]).

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