Is EYS p.Ala1591Val (c.4772C>T) pathogenic?

EYS p.Ala1591Val (c.4772C>T) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.1604); Very rare (popmax 0.00244%, eas); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Ala1591Val (c.4772C>T)?

EYS p.Ala1591Val (c.4772C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Ala1591Val (c.4772C>T) in the general population?

EYS p.Ala1591Val (c.4772C>T) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about EYS p.Ala1591Val (c.4772C>T)?

AlphaMissense predicts likely benign (score 0.1604) — an in-silico prediction, not a clinical call.

EYS p.Ala1591Val

c.4772C>T · rs754252474 · VCV2411143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1604	likely benign
REVEL	0.302	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	12.73	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 0.00244% East Asian · 1/40,916 alleles

Filtering AF 0.000981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000809%

Overall 0.00129% 20/1,551,090 alleles · very rare exomes 19/1,399,022 · genomes 1/152,068 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,916
European (non-Finnish)	0.00157%	63,710
African / African-American	0.00137%	73,010

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.Ala1591Val
Coding: c.4772C>T
MANE Select: NM_001142800
dbSNP: rs754252474
Type: single nucleotide variant
Location: chr6:64591095 (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.Ala1591= 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-ala1591val (accessed [today's date]).

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