Is EYS p.Ser2191Ile (c.6572G>T) pathogenic?

EYS p.Ser2191Ile (c.6572G>T) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.2638); No allele count reported in gnomAD v4.1 (AN 1,509,758); Associated with inherited retinal dystrophy.

What condition is associated with EYS p.Ser2191Ile (c.6572G>T)?

EYS p.Ser2191Ile (c.6572G>T) is associated with inherited retinal dystrophy (ClinVar).

How common is EYS p.Ser2191Ile (c.6572G>T) in the general population?

EYS p.Ser2191Ile (c.6572G>T) is no allele count reported in gnomAD v4.1 (AN 1,509,758) (gnomAD).

What do computational predictors say about EYS p.Ser2191Ile (c.6572G>T)?

AlphaMissense predicts likely benign (score 0.2638) — an in-silico prediction, not a clinical call.

EYS p.Ser2191Ile

c.6572G>T · rs1771377862 · VCV3027789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2638 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,509,758)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2638	likely benign
REVEL	0.354	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Pangolin	Δ0.22	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.49	GERP 1.4, phastCons 0.17
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	21.3	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

No allele count reported in gnomAD v4.1 (AN 1,509,758). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EYS
Protein: p.Ser2191Ile
Coding: c.6572G>T
MANE Select: NM_001142800
dbSNP: rs1771377862
Type: single nucleotide variant
Location: chr6:64066491 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2191: the laminin g-like 2 domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYS p.Ser2191Asn Uncertain significance ★ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1299+1G>T 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.3243+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.5836-1G>C Pathogenic/Likely pathogenic ★★ same condition
EYS c.6191+2T>C 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-ser2191ile (accessed [today's date]).

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