Is EYS p.Ser2419= (c.7257T>C) pathogenic?

EYS p.Ser2419= (c.7257T>C) is classified Likely benign in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0501%, mid); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Ser2419= (c.7257T>C)?

EYS p.Ser2419= (c.7257T>C) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Ser2419= (c.7257T>C) in the general population?

EYS p.Ser2419= (c.7257T>C) is ultra-rare (popmax 0.0501%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Ser2419=

c.7257T>C · rs768229148 · VCV740371

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0501%, mid)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.96	GERP -3.6
Overall
CADD	2.695	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0501% Middle Eastern · 3/5,984 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00407% 63/1,549,650 alleles · ultra-rare exomes 53/1,397,284 · genomes 10/152,366 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0501%	1,995
South Asian	0.0155%	6,448
Admixed American	0.00984%	10,162
Remaining individualsnot grpmax-eligible	0.00832%	12,020
European (non-Finnish)	0.00323%	30,961

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.Ser2419=
Coding: c.7257T>C
MANE Select: NM_001142800
dbSNP: rs768229148
Type: single nucleotide variant
Location: chr6:63806344 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2419: the laminin g-like 3 domain

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 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
EYS c.1299+2T>A Likely pathogenic ★★ same condition
EYS c.1599+1G>T 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-ser2419 (accessed [today's date]).

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