Is EYS p.Leu3055fs (c.9163_9164del) pathogenic?

EYS p.Leu3055fs (c.91639164del) is classified Likely pathogenic in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-20). Very rare (popmax 0.000349%, nfe); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Leu3055fs (c.9163_9164del)?

EYS p.Leu3055fs (c.9163_9164del) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Leu3055fs (c.9163_9164del) in the general population?

EYS p.Leu3055fs (c.9163_9164del) is very rare (popmax 0.000349%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EYS p.Leu3055fs

c.9163_9164del · rs927327659 · VCV2675299

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (43 of 43) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 0.27, phastCons 0.62
Overall
CADD	33.0	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 0.000349% European (non-Finnish) · 4/1,146,630 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000258% 4/1,551,074 alleles · very rare exomes 2/1,398,972 · genomes 2/152,102 · joint denominator

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: EYS
Protein: p.Leu3055fs
Coding: c.9163_9164del
MANE Select: NM_001142800
dbSNP: rs927327659
Type: Microsatellite
Location: chr6:63720867 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 3055: the laminin g-like 5 domain

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

Disease context

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

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

EYS c.1299+5_1299+8del Pathogenic/Likely pathogenic ★★ same condition
EYS p.Arg1537fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Arg3027fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn2044fs Pathogenic ★★ same condition
EYS p.Asn3015delinsIleTer Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn3061fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Cys1001_Glu1002delinsTer Pathogenic/Likely pathogenic ★★ same condition
EYS p.Cys405_Glu406delinsTer Likely 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/eys-p-leu3055fs (accessed [today's date]).

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