Is EYS p.Glu641Val (c.1922A>T) pathogenic?

EYS p.Glu641Val (c.1922A>T) is classified Benign/Likely benign in EYS (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1718); Common (popmax 21.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with inherited retinal dystrophy.

What condition is associated with EYS p.Glu641Val (c.1922A>T)?

EYS p.Glu641Val (c.1922A>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 25, retinitis pigmentosa (ClinVar).

What do computational predictors say about EYS p.Glu641Val (c.1922A>T)?

AlphaMissense predicts likely benign (score 0.1718) — an in-silico prediction, not a clinical call.

EYS p.Glu641Val

Q: How common is EYS p.Glu641Val (c.1922A>T) in the general population?

EYS p.Glu641Val (c.1922A>T) is common (popmax 21.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1922A>T · rs17411795 · VCV137268

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1718 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1718	likely benign
REVEL	0.395	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -2.7, phastCons 0.007
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	13.67	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 21.6% European (non-Finnish) · 247,570/1,146,458 alleles

Filtering AF 21.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.5%

Overall 19.6% 304,166/1,551,002 alleles · common exomes 279,555/1,399,088 · genomes 24,611/151,914 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	28%	4
European (non-Finnish)grpmax	21.6%	5
Ashkenazi Jewishnot grpmax-eligible	20.9%	5
Remaining individualsnot grpmax-eligible	18%	6
Middle Eastern	14.4%	7
Admixed American	12.6%	8
Amishnot grpmax-eligible	11%	9
South Asian	8.89%	11
East Asian	7.19%	14
African / African-American	7.11%	14

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu641Val
Coding: c.1922A>T
MANE Select: NM_001142800
dbSNP: rs17411795
Type: single nucleotide variant
Location: chr6:65295964 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 641: a UniProt-annotated variant site (in)

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

Also linked: retinitis pigmentosa 25 retinitis pigmentosa

Similar variants

EYS p.Glu641= 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+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-glu641val (accessed [today's date]).

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