Is EYS p.Asp733= (c.2199C>T) pathogenic?

EYS p.Asp733= (c.2199C>T) is classified Likely benign in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). Ultra-rare (popmax 0.0375%, nfe); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Asp733= (c.2199C>T)?

EYS p.Asp733= (c.2199C>T) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Asp733= (c.2199C>T) in the general population?

EYS p.Asp733= (c.2199C>T) is ultra-rare (popmax 0.0375%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Asp733=

c.2199C>T · rs769923713 · VCV788859

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0375%, nfe)

Conditions

retinitis pigmentosa

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 0.6	GERP -0.76
Overall
CADD	4.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0375% European (non-Finnish) · 430/1,146,448 alleles

Filtering AF 0.0346% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.0286% 443/1,550,978 alleles · ultra-rare exomes 426/1,398,802 · genomes 17/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0375%	2,666
Remaining individualsnot grpmax-eligible	0.0166%	6,009
Admixed American	0.00392%	25,484
African / African-American	0.00137%	73,038

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.Asp733=
Coding: c.2199C>T
MANE Select: NM_001142800
dbSNP: rs769923713
Type: single nucleotide variant
Location: chr6:64997642 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 733: the egf-like 9; calcium-binding 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 p.Asp733His Uncertain significance ★ same residue
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

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-asp733 (accessed [today's date]).

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