Is EYS p.Asp546= (c.1638C>T) pathogenic?

EYS p.Asp546= (c.1638C>T) is classified Likely benign in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.123%, afr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Asp546= (c.1638C>T)?

EYS p.Asp546= (c.1638C>T) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Asp546= (c.1638C>T) in the general population?

EYS p.Asp546= (c.1638C>T) is rare (popmax 0.123%, 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.Asp546=

c.1638C>T · rs373584729 · VCV1080545

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.9	GERP -2.3
Overall
CADD	0.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% African / African-American · 92/74,864 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.095%

Overall 0.00658% 106/1,611,766 alleles · rare exomes 52/1,459,944 · genomes 54/151,822 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	814
Admixed American	0.0134%	7,465
Remaining individualsnot grpmax-eligible	0.00962%	10,396

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.Asp546=
Coding: c.1638C>T
MANE Select: NM_001142800
dbSNP: rs373584729
Type: single nucleotide variant
Location: chr6:65335108 (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 p.Asp546fs Pathogenic/Likely pathogenic ★★ same residue
EYS p.Asp546Glu Uncertain significance ★ ⚠ same residue
EYS p.Asp546Gly 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

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-asp546 (accessed [today's date]).

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