Is EYS p.Asp854= (c.2562C>T) pathogenic?

EYS p.Asp854= (c.2562C>T) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.258%, afr); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Asp854= (c.2562C>T)?

EYS p.Asp854= (c.2562C>T) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Asp854= (c.2562C>T) in the general population?

EYS p.Asp854= (c.2562C>T) is rare (popmax 0.258%, 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.Asp854=

c.2562C>T · rs188011013 · VCV357728

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, afr)

Conditions

retinitis pigmentosa

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 0.55
Overall
CADD	0.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% African / African-American · 189/73,120 alleles

Filtering AF 0.228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.217%

Overall 0.0138% 214/1,551,234 alleles · rare exomes 102/1,399,022 · genomes 112/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.258%	387
Admixed American	0.0216%	4,635
Remaining individualsnot grpmax-eligible	0.02%	5,008
European (non-Finnish)	0.000174%	573,322

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.Asp854=
Coding: c.2562C>T
MANE Select: NM_001142800
dbSNP: rs188011013
Type: single nucleotide variant
Location: chr6:64912563 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 854: the egf-like 12 domain

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

Disease context

retinitis pigmentosa — 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 c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1766+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.2259+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3164+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3243+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3443+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928-2A>G Pathogenic ★★ same condition
EYS c.6191+2T>C 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-asp854 (accessed [today's date]).

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