Is EYS p.Thr2fs (c.-40_3dup) pathogenic?

EYS p.Thr2fs (c.-403dup) is classified Likely pathogenic in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-18). No gnomAD frequency available for this variant; Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Thr2fs (c.-40_3dup)?

EYS p.Thr2fs (c.-40_3dup) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Thr2fs (c.-40_3dup) in the general population?

EYS p.Thr2fs (c.-40_3dup) 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.Thr2fs

c.-40_3dup · rs2533031069 · VCV2675329

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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 4 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP -1.2, phastCons 0.93

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.Thr2fs
Coding: c.-40_3dup
MANE Select: NM_001142800
dbSNP: rs2533031069
Type: Duplication
Location: chr6:65495407 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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.2021_2023+1dup Likely pathogenic ★★ same condition
EYS p.Arg3094fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn2803fs Pathogenic ★★ same condition
EYS p.Asn443fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn654fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Cys952fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Gln27fs Pathogenic ★★ same condition
EYS p.Glu1830fs 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-thr2fs (accessed [today's date]).

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