Is EYS p.Cys1982Arg (c.5944T>C) pathogenic?

EYS p.Cys1982Arg (c.5944T>C) is classified Uncertain significance in EYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-02-15). AlphaMissense: likely pathogenic (0.8369); Very rare (popmax 0.0013%, sas).

How common is EYS p.Cys1982Arg (c.5944T>C) in the general population?

EYS p.Cys1982Arg (c.5944T>C) is very rare (popmax 0.0013%, sas) (gnomAD).

What do computational predictors say about EYS p.Cys1982Arg (c.5944T>C)?

AlphaMissense predicts likely pathogenic (score 0.8369) — an in-silico prediction, not a clinical call.

EYS p.Cys1982Arg

c.5944T>C · rs377025352 · VCV2165870

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0013%, sas)

Computational evidence

Protein change
AlphaMissense	0.8369	likely pathogenic · top 4% in EYS
REVEL	0.437	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.017, phastCons 0.17
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	21.6	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 0.0013% South Asian · 1/76,660 alleles

Filtering AF 0.00019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000125%

Overall 0.00046% 7/1,521,878 alleles · very rare exomes 7/1,369,576 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0013%	76,660
European (non-Finnish)	0.000529%	188,972

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.Cys1982Arg
Coding: c.5944T>C
MANE Select: NM_001142800
dbSNP: rs377025352
Type: single nucleotide variant
Location: chr6:64388824 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 1982: the laminin g-like 1 domain

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

Similar variants

EYS p.Cys1982Phe Uncertain significance ★★ same residue
EYS p.Cys1982Tyr Uncertain significance ★ 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
EYS c.1184+1G>A Pathogenic/Likely pathogenic ★★ same type
EYS c.1184+1G>T Likely pathogenic ★★ same type
EYS c.1185-1G>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-cys1982arg (accessed [today's date]).

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