Is EYS p.Pro75Arg (c.224C>G) pathogenic?

EYS p.Pro75Arg (c.224C>G) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-25). AlphaMissense: likely benign (0.3185); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EYS p.Pro75Arg (c.224C>G)?

EYS p.Pro75Arg (c.224C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Pro75Arg (c.224C>G) in the general population?

EYS p.Pro75Arg (c.224C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EYS p.Pro75Arg (c.224C>G)?

AlphaMissense predicts likely benign (score 0.3185) — an in-silico prediction, not a clinical call.

EYS p.Pro75Arg

c.224C>G · rs1766205632 · VCV2075885

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3185 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3185	likely benign
REVEL	0.462	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.16, phastCons 0.42
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	18.72	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EYS
Protein: p.Pro75Arg
Coding: c.224C>G
MANE Select: NM_001142800
dbSNP: rs1766205632
Type: single nucleotide variant
Location: chr6:65495187 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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.Pro75= 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
EYS p.Ala2729Val 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-pro75arg (accessed [today's date]).

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