Is EYS p.Pro1306= (c.3918A>T) pathogenic?

EYS p.Pro1306= (c.3918A>T) is classified Likely benign in EYS (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-21). Very rare (popmax 0.000619%, nfe); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Pro1306= (c.3918A>T)?

EYS p.Pro1306= (c.3918A>T) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Pro1306= (c.3918A>T) in the general population?

EYS p.Pro1306= (c.3918A>T) is very rare (popmax 0.000619%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Pro1306=

c.3918A>T · rs997369455 · VCV1098192

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000619%, nfe)

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 2.3	GERP 2.4, phastCons 0.083
Overall
CADD	4.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000619% European (non-Finnish) · 7/1,130,574 alleles

Filtering AF 0.000257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00046% 7/1,522,230 alleles · very rare exomes 6/1,370,122 · genomes 1/152,108 · joint denominator

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.Pro1306=
Coding: c.3918A>T
MANE Select: NM_001142800
dbSNP: rs997369455
Type: single nucleotide variant
Location: chr6:64591949 (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-pro1306 (accessed [today's date]).

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