Is EYS p.Ser547fs (c.1641_1644del) pathogenic?

EYS p.Ser547fs (c.16411644del) is classified Pathogenic in EYS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-15). Very rare (popmax 0.00134%, afr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Ser547fs (c.1641_1644del)?

EYS p.Ser547fs (c.1641_1644del) is associated with retinitis pigmentosa 25 (ClinVar).

How common is EYS p.Ser547fs (c.1641_1644del) in the general population?

EYS p.Ser547fs (c.1641_1644del) is very rare (popmax 0.00134%, 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.Ser547fs

c.1641_1644del · rs752504462 · VCV1070910

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.6	GERP -0.47

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,880 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,611,910 alleles · very rare exomes 7/1,460,090 · genomes 0/151,820 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,880
European (non-Finnish)	0.000509%	196,469

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.Ser547fs
Coding: c.1641_1644del
MANE Select: NM_001142800
dbSNP: rs752504462
Type: Deletion
Location: chr6:65335102 (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.1057del Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928-3_5928-1del Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928del Pathogenic ★★ same condition
EYS c.6079-3_6079-2del Pathogenic/Likely pathogenic ★★ same condition
EYS c.749del Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala1520fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala1557fs Pathogenic/Likely pathogenic ★★ same condition
EYS p.Ala2957fs Pathogenic/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-ser547fs (accessed [today's date]).

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