Is EYS p.Pro994fs (c.2981del) pathogenic?

EYS p.Pro994fs (c.2981del) is classified Pathogenic in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-18). No gnomAD frequency available for this variant; Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Pro994fs (c.2981del)?

EYS p.Pro994fs (c.2981del) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Pro994fs (c.2981del) in the general population?

EYS p.Pro994fs (c.2981del) is no gnomAD frequency available for this variant (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Pro994fs

c.2981del · rs1583260302 · VCV802237

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 19 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.49, phastCons 0.002

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EYS
Protein: p.Pro994fs
Coding: c.2981del
MANE Select: NM_001142800
dbSNP: rs1583260302
Type: Deletion
Location: chr6:64886708 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 994: the egf-like 15 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.1057del Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928-3_5928-1del Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928del Pathogenic ★★ same condition
EYS c.6079-3_6079-2del Pathogenic/Likely pathogenic ★★ same condition
EYS c.749del Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala1520fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala1557fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala2957fs Pathogenic/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-pro994fs (accessed [today's date]).

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