Is EYS p.Ser1342= (c.4026C>T) pathogenic?

EYS p.Ser1342= (c.4026C>T) is classified Benign in EYS (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 14.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with EYS p.Ser1342= (c.4026C>T)?

EYS p.Ser1342= (c.4026C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 25, retinitis pigmentosa (ClinVar).

EYS p.Ser1342=

Q: How common is EYS p.Ser1342= (c.4026C>T) in the general population?

EYS p.Ser1342= (c.4026C>T) is common (popmax 14.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4026C>T · rs12663619 · VCV93609

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 14.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

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 0.072	GERP -0.9
Overall
CADD	9.486	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.7% East Asian · 6,018/40,872 alleles

Filtering AF 14.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.3%

Overall 12.9% 200,111/1,550,060 alleles · common exomes 184,760/1,397,980 · genomes 15,351/152,080 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	14.7%	7
European (non-Finnish)	14.1%	7
Admixed American	13.2%	8
Remaining individualsnot grpmax-eligible	12.3%	8
Amishnot grpmax-eligible	10.5%	10
South Asian	10.5%	10
Finnishnot grpmax-eligible	7.95%	13
Ashkenazi Jewishnot grpmax-eligible	7.87%	13
Middle Eastern	5.81%	17
African / African-American	3.37%	30

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.Ser1342=
Coding: c.4026C>T
MANE Select: NM_001142800
dbSNP: rs12663619
Type: single nucleotide variant
Location: chr6:64591841 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 25 retinitis pigmentosa

Similar variants

EYS p.Ser1342Phe Uncertain significance ★ ⚠ same residue
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+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-ser1342 (accessed [today's date]).

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