Is EYS p.Phe53Leu (c.159C>G) pathogenic?

EYS p.Phe53Leu (c.159C>G) is classified Uncertain significance in EYS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-08-14). AlphaMissense: likely pathogenic (0.8055); Absent from gnomAD v4.1; Associated with Autosomal recessive retinitis pigmentosa.

What condition is associated with EYS p.Phe53Leu (c.159C>G)?

EYS p.Phe53Leu (c.159C>G) is associated with Autosomal recessive retinitis pigmentosa (ClinVar).

How common is EYS p.Phe53Leu (c.159C>G) in the general population?

EYS p.Phe53Leu (c.159C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYS p.Phe53Leu (c.159C>G)?

AlphaMissense predicts likely pathogenic (score 0.8055) — an in-silico prediction, not a clinical call.

EYS p.Phe53Leu

c.159C>G · rs1766211185 · VCV991149

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8055 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Autosomal recessive retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.8055	likely pathogenic · top 5% in EYS
REVEL	0.178	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.052	GERP 0.15
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EYS
Protein: p.Phe53Leu
Coding: c.159C>G
MANE Select: NM_001142800
dbSNP: rs1766211185
Type: single nucleotide variant
Location: chr6:65495252 (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

Autosomal recessive retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYS p.Phe53= Likely benign ★ same residue
EYS c.1767-6T>C Uncertain significance same condition
EYS p.Ala1112Val Uncertain significance ⚠ same condition
EYS p.Arg589Lys Uncertain significance same condition
EYS p.Asn2354Lys Uncertain significance ⚠ same condition
EYS p.Asp750His Uncertain significance same condition
EYS p.Glu2585Lys Uncertain significance ⚠ same condition
EYS p.Glu30Gly Uncertain significance ⚠ 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-phe53leu (accessed [today's date]).

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