Is EYS p.Pro94Gln (c.281C>A) pathogenic?

EYS p.Pro94Gln (c.281C>A) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2084); Low-frequency (popmax 1.4%, afr); Associated with retinitis pigmentosa 25.

What condition is associated with EYS p.Pro94Gln (c.281C>A)?

EYS p.Pro94Gln (c.281C>A) is associated with retinitis pigmentosa 25, retinitis pigmentosa (ClinVar).

How common is EYS p.Pro94Gln (c.281C>A) in the general population?

EYS p.Pro94Gln (c.281C>A) is low-frequency (popmax 1.4%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about EYS p.Pro94Gln (c.281C>A)?

AlphaMissense predicts likely benign (score 0.2084) — an in-silico prediction, not a clinical call.

EYS p.Pro94Gln

c.281C>A · rs111947397 · VCV357749

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.2084 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.4%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

retinitis pigmentosa 25

Computational evidence

Protein change
AlphaMissense	0.2084	likely benign
REVEL	0.207	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP -1.6, phastCons 0.025
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	17.92	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

Grpmax group 1.4% African / African-American · 1,050/75,012 alleles

Filtering AF 1.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 0.0901% 1,454/1,614,048 alleles · low-frequency exomes 838/1,461,746 · genomes 616/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.4%	71
Middle Eastern	0.231%	433
Admixed American	0.182%	550
Remaining individualsnot grpmax-eligible	0.139%	718
European (non-Finnish)	0.0156%	6,413
South Asian	0.00988%	10,120
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Pro94Gln
Coding: c.281C>A
MANE Select: NM_001142800
dbSNP: rs111947397
Type: single nucleotide variant
Location: chr6:65495130 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 94: a UniProt-annotated variant site (in)

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

Also linked: retinitis pigmentosa

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.Pro94= Likely benign ★ 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
EYS c.1185-1G>A Likely pathogenic ★★ same condition
EYS c.1299+2T>A 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-pro94gln (accessed [today's date]).

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