Is EYS p.Cys813= (c.2439C>T) pathogenic?

EYS p.Cys813= (c.2439C>T) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-18). Ultra-rare (popmax 0.054%, afr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Cys813= (c.2439C>T)?

EYS p.Cys813= (c.2439C>T) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Cys813= (c.2439C>T) in the general population?

EYS p.Cys813= (c.2439C>T) is ultra-rare (popmax 0.054%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EYS p.Cys813=

c.2439C>T · rs367546131 · VCV835210

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.054%, afr)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	phastCons 0.97
Overall
CADD	9.152	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.054% African / African-American · 39/72,248 alleles

Filtering AF 0.0406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0359%

Overall 0.00611% 93/1,522,754 alleles · ultra-rare exomes 67/1,370,622 · genomes 26/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.054%	1,853
Middle Eastern	0.0342%	2,922
Admixed American	0.0082%	12,192
Remaining individualsnot grpmax-eligible	0.00681%	14,692
East Asian	0.00495%	20,210
South Asian	0.00372%	26,870
Ashkenazi Jewishnot grpmax-eligible	0.00367%	27,278
European (non-Finnish)	0.00337%	29,709

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.Cys813=
Coding: c.2439C>T
MANE Select: NM_001142800
dbSNP: rs367546131
Type: single nucleotide variant
Location: chr6:64912686 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 813: the egf-like 11 domain; a disulfide bond

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

Disease context

retinitis pigmentosa 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

EYS p.Cys813Ter Pathogenic ★★ same residue
EYS p.Cys813Arg Uncertain significance same residue
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

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-cys813 (accessed [today's date]).

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