Is EYS p.Ser2274= (c.6822C>A) pathogenic?

EYS p.Ser2274= (c.6822C>A) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-23). Very rare (popmax 0.00685%, afr); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Ser2274= (c.6822C>A)?

EYS p.Ser2274= (c.6822C>A) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Ser2274= (c.6822C>A) in the general population?

EYS p.Ser2274= (c.6822C>A) is very rare (popmax 0.00685%, 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.Ser2274=

c.6822C>A · rs1055095941 · VCV762632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00685%, afr)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.018	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.071	GERP -3.2
Overall
CADD	0.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00685% African / African-American · 5/72,950 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00413% 64/1,548,930 alleles · very rare exomes 60/1,396,798 · genomes 4/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00685%	14,590
Remaining individualsnot grpmax-eligible	0.00665%	15,031
European (non-Finnish)	0.00481%	20,806

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.Ser2274=
Coding: c.6822C>A
MANE Select: NM_001142800
dbSNP: rs1055095941
Type: single nucleotide variant
Location: chr6:63999087 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2274: the laminin g-like 2 domain

Full EYS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa — 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.Ser2274Cys Uncertain significance ⚠ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1766+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.2259+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3164+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3243+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3443+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928-2A>G 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-ser2274 (accessed [today's date]).

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