Is EYS p.Cys1996= (c.5988C>T) pathogenic?

EYS p.Cys1996= (c.5988C>T) is classified Likely benign in EYS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-06). Ultra-rare (popmax 0.0714%, afr); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Cys1996= (c.5988C>T)?

EYS p.Cys1996= (c.5988C>T) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Cys1996= (c.5988C>T) in the general population?

EYS p.Cys1996= (c.5988C>T) is ultra-rare (popmax 0.0714%, 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.Cys1996=

c.5988C>T · rs370988507 · VCV710964

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, afr)

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 -4.9	GERP -2.6
Overall
CADD	0.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0714% African / African-American · 52/72,832 alleles

Filtering AF 0.0559% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0504%

Overall 0.00492% 76/1,543,592 alleles · ultra-rare exomes 36/1,391,556 · genomes 40/152,036 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0714%	1,401
Remaining individualsnot grpmax-eligible	0.00502%	19,911
South Asian	0.00364%	27,485
East Asian	0.00248%	40,378
European (non-Finnish)	0.00149%	67,231

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.Cys1996=
Coding: c.5988C>T
MANE Select: NM_001142800
dbSNP: rs370988507
Type: single nucleotide variant
Location: chr6:64388780 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 1996: the laminin g-like 1 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.Cys1996Ter Pathogenic/Likely pathogenic ★★ 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-cys1996 (accessed [today's date]).

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