Is EYS p.Val1362= (c.4086C>A) pathogenic?

EYS p.Val1362= (c.4086C>A) is classified Likely benign in EYS (ClinVar, Single submitter, 2 submitters; last evaluated 2023-06-05). Very rare (popmax 0.00589%, amr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Val1362= (c.4086C>A)?

EYS p.Val1362= (c.4086C>A) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Val1362= (c.4086C>A) in the general population?

EYS p.Val1362= (c.4086C>A) is very rare (popmax 0.00589%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Val1362=

c.4086C>A · rs1766419897 · VCV1648663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00589%, amr)

Conditions

retinitis pigmentosa 25

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 1.3	phastCons 0.002
Overall
CADD	0.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00589% Admixed American · 3/50,974 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.000838% 13/1,551,276 alleles · very rare exomes 13/1,399,084 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00589%	16,991
Remaining individualsnot grpmax-eligible	0.00333%	30,052
European (non-Finnish)	0.000698%	143,340

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.Val1362=
Coding: c.4086C>A
MANE Select: NM_001142800
dbSNP: rs1766419897
Type: single nucleotide variant
Location: chr6:64591781 (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

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-val1362 (accessed [today's date]).

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