Is EYS p.His201Arg (c.602A>G) pathogenic?

EYS p.His201Arg (c.602A>G) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1144); Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with EYS p.His201Arg (c.602A>G)?

EYS p.His201Arg (c.602A>G) is associated with Inborn genetic diseases, retinitis pigmentosa 25, inherited retinal dystrophy (ClinVar).

How common is EYS p.His201Arg (c.602A>G) in the general population?

EYS p.His201Arg (c.602A>G) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about EYS p.His201Arg (c.602A>G)?

AlphaMissense predicts likely benign (score 0.1144) — an in-silico prediction, not a clinical call.

EYS p.His201Arg

c.602A>G · rs1011260787 · VCV624255

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1144 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1144	likely benign
REVEL	0.117	moderately 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 0.39	GERP -1.1, phastCons 0.98
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	6.866	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00062% 10/1,614,084 alleles · ultra-rare exomes 10/1,461,816 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.000254%	393,338

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.His201Arg
Coding: c.602A>G
MANE Select: NM_001142800
dbSNP: rs1011260787
Type: single nucleotide variant
Location: chr6:65494809 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 201: the egf-like 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 25 inherited retinal dystrophy

Similar variants

EYS p.His201Tyr 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
EYS c.1185-1G>A Likely pathogenic ★★ same condition
EYS c.1299+1G>T 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-his201arg (accessed [today's date]).

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