Is EYS p.Gln259= (c.777G>A) pathogenic?

EYS p.Gln259= (c.777G>A) is classified Benign/Likely benign in EYS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.82%, afr); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Gln259= (c.777G>A)?

EYS p.Gln259= (c.777G>A) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Gln259= (c.777G>A) in the general population?

EYS p.Gln259= (c.777G>A) is low-frequency (popmax 3.82%, 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.Gln259=

c.777G>A · rs78079047 · VCV357745

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.82%, 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 -7.6	GERP -2.9
Overall
CADD	0.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.82% African / African-American · 2,859/74,932 alleles

Filtering AF 3.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.65%

Overall 0.201% 3,239/1,612,266 alleles · low-frequency exomes 1,602/1,460,128 · genomes 1,637/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.82%	26
Remaining individualsnot grpmax-eligible	0.256%	390
Admixed American	0.227%	441
Middle Eastern	0.182%	550
South Asian	0.011%	9,100
European (non-Finnish)	0.00534%	18,710

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.Gln259=
Coding: c.777G>A
MANE Select: NM_001142800
dbSNP: rs78079047
Type: single nucleotide variant
Location: chr6:65490679 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 259: the egf-like 3 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.Gln259Ter Pathogenic/Likely pathogenic ★★ same residue
EYS p.Gln259His 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

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-gln259 (accessed [today's date]).

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