Is EYS p.Val944fs (c.2826_2827del) pathogenic?

EYS p.Val944fs (c.28262827del) is classified Pathogenic in EYS (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-04). Very rare (popmax 0.0028%, nfe); Associated with EYS-related disorder.

What condition is associated with EYS p.Val944fs (c.2826_2827del)?

EYS p.Val944fs (c.2826_2827del) is associated with EYS-related disorder, retinitis pigmentosa 25, inherited retinal dystrophy (ClinVar).

How common is EYS p.Val944fs (c.2826_2827del) in the general population?

EYS p.Val944fs (c.2826_2827del) is very rare (popmax 0.0028%, nfe) (gnomAD).

EYS p.Val944fs

c.2826_2827del · rs878853349 · VCV236446

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0028%, 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 18 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.059	phastCons 0.001
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% European (non-Finnish) · 32/1,144,542 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00173%

Overall 0.0022% 34/1,545,908 alleles · very rare exomes 33/1,393,814 · genomes 1/152,094 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,767
Remaining individualsnot grpmax-eligible	0.00167%	59,906
African / African-American	0.00138%	72,710

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.Val944fs
Coding: c.2826_2827del
MANE Select: NM_001142800
dbSNP: rs878853349
Type: Deletion
Location: chr6:64902132 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 944: the egf-like 14; calcium-binding domain

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

Disease context

EYS-related disorder

Also linked: retinitis pigmentosa 25 inherited retinal dystrophy retinitis pigmentosa

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-val944fs (accessed [today's date]).

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