Is EYS p.Pro2600fs (c.7798_7802del) pathogenic?

EYS p.Pro2600fs (c.77987802del) is classified Pathogenic/Likely pathogenic in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-05). Very rare (popmax 0.000349%, nfe); Associated with EYS-related disorder.

What condition is associated with EYS p.Pro2600fs (c.7798_7802del)?

EYS p.Pro2600fs (c.7798_7802del) is associated with EYS-related disorder (ClinVar).

How common is EYS p.Pro2600fs (c.7798_7802del) in the general population?

EYS p.Pro2600fs (c.7798_7802del) is very rare (popmax 0.000349%, nfe) (gnomAD).

EYS p.Pro2600fs

c.7798_7802del · rs1770112191 · VCV1451460

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Conditions

EYS-related disorder

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 40 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.095	GERP -1.3

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) · 4/1,146,956 alleles

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

Overall 0.000258% 4/1,551,788 alleles · very rare exomes 4/1,399,440 · genomes 0/152,348 · 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.Pro2600fs
Coding: c.7798_7802del
MANE Select: NM_001142800
dbSNP: rs1770112191
Type: Deletion
Location: chr6:63778102 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2600: the laminin g-like 3 domain

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

Disease context

EYS-related disorder

Similar variants

EYS p.Ala2957fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn1773_Val1781delinsLys Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn2918fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Asn328fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Cys412fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Cys78fs Pathogenic ★★ same condition
EYS p.Gln2723fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Gln3053fs 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-pro2600fs (accessed [today's date]).

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