Is EYS p.Ala504= (c.1512T>A) pathogenic?

EYS p.Ala504= (c.1512T>A) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0642%, afr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Ala504= (c.1512T>A)?

EYS p.Ala504= (c.1512T>A) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Ala504= (c.1512T>A) in the general population?

EYS p.Ala504= (c.1512T>A) is ultra-rare (popmax 0.0642%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

EYS p.Ala504=

c.1512T>A · rs142178909 · VCV799476

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0642%, afr)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.62	acceptor gain · deltas
Pangolin	Δ0.23	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.41	GERP -0.4
Overall
CADD	16.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0642% African / African-American · 48/74,810 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0445%

Overall 0.00416% 67/1,610,708 alleles · ultra-rare exomes 28/1,459,060 · genomes 39/151,648 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0642%	1,559
Admixed American	0.0201%	4,974
Remaining individualsnot grpmax-eligible	0.0112%	8,902

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.Ala504=
Coding: c.1512T>A
MANE Select: NM_001142800
dbSNP: rs142178909
Type: single nucleotide variant
Location: chr6:65344125 (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-ala504 (accessed [today's date]).

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