Is EYS p.Ser195Arg (c.585C>G) pathogenic?

EYS p.Ser195Arg (c.585C>G) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-06). AlphaMissense: likely benign (0.2873); Very rare (popmax 0.00381%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Ser195Arg (c.585C>G)?

EYS p.Ser195Arg (c.585C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Ser195Arg (c.585C>G) in the general population?

EYS p.Ser195Arg (c.585C>G) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about EYS p.Ser195Arg (c.585C>G)?

AlphaMissense predicts likely benign (score 0.2873) — an in-silico prediction, not a clinical call.

EYS p.Ser195Arg

c.585C>G · rs764334169 · VCV2154710

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2873	likely benign
REVEL	0.32	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP -2.9, phastCons 0.1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	7.776	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 0.00381% European (non-Finnish) · 45/1,179,982 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00285% 46/1,613,874 alleles · very rare exomes 45/1,461,820 · genomes 1/152,054 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,222
African / African-American	0.00134%	74,886

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.Ser195Arg
Coding: c.585C>G
MANE Select: NM_001142800
dbSNP: rs764334169
Type: single nucleotide variant
Location: chr6:65494826 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 195: 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

Similar variants

EYS p.Ser195Asn Uncertain significance ★ ⚠ same residue
EYS p.Ser195= Likely benign ★ same residue
EYS p.Ala1174Glu Uncertain significance ★★ same condition
EYS p.Ala1465Thr Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Asp Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Gly Uncertain significance ★★ ⚠ same condition
EYS p.Ala1984Thr Uncertain significance ★★ same condition
EYS p.Ala2728Val Uncertain significance ★★ ⚠ 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-ser195arg (accessed [today's date]).

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