Is CEP290 p.Arg1271Ter (c.3811C>T) pathogenic?

CEP290 p.Arg1271Ter (c.3811C>T) is classified Pathogenic in CEP290 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2024-07-23). Very rare (popmax 0.00134%, afr); Associated with CEP290-related disorder.

What condition is associated with CEP290 p.Arg1271Ter (c.3811C>T)?

CEP290 p.Arg1271Ter (c.3811C>T) is associated with CEP290-related disorder, Meckel syndrome, type 4, Bardet-Biedl syndrome 14 (ClinVar).

How common is CEP290 p.Arg1271Ter (c.3811C>T) in the general population?

CEP290 p.Arg1271Ter (c.3811C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CEP290 p.Arg1271Ter

c.3811C>T · rs1412133967 · VCV950504

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

CEP290-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 31 of 54
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	phastCons 1
Overall
CADD	38.0	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 0.00134% African / African-American · 1/74,902 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,613,738 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,902
European (non-Finnish)	0.000763%	131,094

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: CEP290
Protein: p.Arg1271Ter
Coding: c.3811C>T
MANE Select: NM_025114
dbSNP: rs1412133967
Type: single nucleotide variant
Location: chr12:88089250 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 1271: a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss); a UniProt-annotated variant site (in lca10)

Full CEP290 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: Meckel syndrome, type 4 Bardet-Biedl syndrome 14 Joubert syndrome Meckel syndrome Leber congenital amaurosis nephronophthisis inherited retinal dystrophy

Similar variants

CEP290 p.Arg1271= Uncertain significance same residue
CEP290 p.Arg1271Gln Uncertain significance ★★ ⚠ same residue
CEP290 c.1189+1G>A Pathogenic ★★★ same condition
CEP290 c.1189+2T>C Pathogenic ★★★ same condition
CEP290 c.297+1G>T Pathogenic ★★★ same condition
CEP290 c.2991+1655A>G Pathogenic ★★★ same condition
CEP290 c.6271-8T>G Pathogenic ★★★ same condition
CEP290 p.Arg1272Ter 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/cep290-p-arg1271ter (accessed [today's date]).

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