Is EYS p.Val603= (c.1809C>T) pathogenic?

EYS p.Val603= (c.1809C>T) is classified Benign/Likely benign in EYS (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 90.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with EYS p.Val603= (c.1809C>T)?

EYS p.Val603= (c.1809C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 25, retinitis pigmentosa (ClinVar).

EYS p.Val603=

Q: How common is EYS p.Val603= (c.1809C>T) in the general population?

EYS p.Val603= (c.1809C>T) is common (popmax 90.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1809C>T · rs9345601 · VCV137266

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 90.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.69	GERP -0.47
Overall
CADD	2.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.8% East Asian · 37,083/40,840 alleles

Filtering AF 90% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.7%

Overall 58.4% 904,230/1,548,970 alleles · common exomes 825,266/1,397,196 · genomes 78,964/151,774 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	90.8%	1
Amishnot grpmax-eligible	73.5%	1
Admixed American	72.2%	1
South Asian	66.1%	2
Remaining individualsnot grpmax-eligible	58.8%	2
European (non-Finnish)	58.3%	2
Finnishnot grpmax-eligible	56.4%	2
Middle Eastern	54.2%	2
Ashkenazi Jewishnot grpmax-eligible	52.1%	2
African / African-American	27.1%	4

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.Val603=
Coding: c.1809C>T
MANE Select: NM_001142800
dbSNP: rs9345601
Type: single nucleotide variant
Location: chr6:65296077 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 25 retinitis pigmentosa

Similar variants

EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1056+3A>C Likely pathogenic ★★ same condition
EYS c.1057-1G>A Likely pathogenic ★★ same condition
EYS c.1184+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1184+1G>T Likely pathogenic ★★ same condition
EYS c.1185-1G>A Likely pathogenic ★★ same condition
EYS c.1299+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.1299+2T>A 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-val603 (accessed [today's date]).

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