Is EYS p.Arg2583= (c.7749C>T) pathogenic?

EYS p.Arg2583= (c.7749C>T) is classified Likely benign in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-28). Very rare (popmax 0.000174%, nfe).

How common is EYS p.Arg2583= (c.7749C>T) in the general population?

EYS p.Arg2583= (c.7749C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

EYS p.Arg2583=

c.7749C>T · rs2149664363 · VCV1150466

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.61	GERP -2, phastCons 0.14
Overall
CADD	14.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,980 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,551,888 alleles · very rare exomes 2/1,399,544 · genomes 0/152,344 · joint denominator

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.Arg2583=
Coding: c.7749C>T
MANE Select: NM_001142800
dbSNP: rs2149664363
Type: single nucleotide variant
Location: chr6:63778155 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 2583: the laminin g-like 3 domain

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

Similar variants

EYS p.Arg2583His Uncertain significance ★★ ⚠ same residue
EYS p.Arg2583Leu Uncertain significance ★★ same residue
EYS p.Arg2583Cys Uncertain significance ★ same residue
EYS p.Arg2583Pro Uncertain significance ★ same residue
EYS p.Arg2583fs Pathogenic ★ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same type
EYS c.1056+3A>C Likely pathogenic ★★ same type
EYS c.1057-1G>A Likely pathogenic ★★ same type

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-arg2583 (accessed [today's date]).

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