Is EYS p.Val3134fs (c.9400del) pathogenic?

EYS p.Val3134fs (c.9400del) is classified Pathogenic/Likely pathogenic in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-01). Very rare (popmax 0.000443%, nfe).

How common is EYS p.Val3134fs (c.9400del) in the general population?

EYS p.Val3134fs (c.9400del) is very rare (popmax 0.000443%, nfe) (gnomAD).

EYS p.Val3134fs

c.9400del · rs886042614 · VCV283385

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 0.000443%, nfe)

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 5.1	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 0.000443% European (non-Finnish) · 5/1,128,138 alleles

Filtering AF 0.00013% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.000331% 5/1,510,858 alleles · very rare exomes 5/1,358,686 · genomes 0/152,172 · 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.Val3134fs
Coding: c.9400del
MANE Select: NM_001142800
dbSNP: rs886042614
Type: Deletion
Location: chr6:63720631 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 3134: the laminin g-like 5 domain

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

Similar variants

EYS p.Val3134Ala Uncertain significance ★ same residue
EYS c.1057del Pathogenic/Likely pathogenic ★★ same type
EYS c.5928-3_5928-1del Pathogenic/Likely pathogenic ★★ same type
EYS c.5928del Pathogenic ★★ same type
EYS c.6079-3_6079-2del Pathogenic/Likely pathogenic ★★ same type
EYS c.749del Pathogenic/Likely pathogenic ★★ same type
EYS p.Ala1520fs Pathogenic/Likely pathogenic ★★ same type
EYS p.Ala1557fs Pathogenic/Likely pathogenic ★★ same type

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-val3134fs (accessed [today's date]).

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