Is EYS p.Lys3111fs (c.9333_9334del) pathogenic?

EYS p.Lys3111fs (c.93339334del) is classified Pathogenic/Likely pathogenic in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). Very rare (popmax 0.000262%, nfe); Associated with EYS-related disorder.

What condition is associated with EYS p.Lys3111fs (c.9333_9334del)?

EYS p.Lys3111fs (c.9333_9334del) is associated with EYS-related disorder (ClinVar).

How common is EYS p.Lys3111fs (c.9333_9334del) in the general population?

EYS p.Lys3111fs (c.9333_9334del) is very rare (popmax 0.000262%, nfe) (gnomAD).

EYS p.Lys3111fs

c.9333_9334del · rs1225788826 · VCV1995288

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000262%, 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	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 6.9	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000262% European (non-Finnish) · 3/1,145,708 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000258% 4/1,548,428 alleles · very rare exomes 4/1,396,304 · genomes 0/152,124 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00167%	59,968
European (non-Finnish)grpmax	0.000262%	381,902

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys3111fs
Coding: c.9333_9334del
MANE Select: NM_001142800
dbSNP: rs1225788826
Type: Deletion
Location: chr6:63720697 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 3111: the laminin g-like 5 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-lys3111fs (accessed [today's date]).

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