Is EYS p.Ala239Val (c.716C>T) pathogenic?

EYS p.Ala239Val (c.716C>T) is classified Conflicting classifications of pathogenicity in EYS (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1244); Rare (popmax 0.227%, afr); Associated with retinitis pigmentosa.

What condition is associated with EYS p.Ala239Val (c.716C>T)?

EYS p.Ala239Val (c.716C>T) is associated with retinitis pigmentosa (ClinVar).

How common is EYS p.Ala239Val (c.716C>T) in the general population?

EYS p.Ala239Val (c.716C>T) is rare (popmax 0.227%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EYS p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

EYS p.Ala239Val

c.716C>T · rs150140204 · VCV755637

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.251	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.5
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	0.372	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 0.227% African / African-American · 168/74,012 alleles

Filtering AF 0.199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.0127% 202/1,587,136 alleles · rare exomes 113/1,434,944 · genomes 89/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.227%	441
Middle Eastern	0.0337%	2,971
Admixed American	0.0264%	3,795
Remaining individualsnot grpmax-eligible	0.0261%	3,831
South Asian	0.00113%	88,146

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.Ala239Val
Coding: c.716C>T
MANE Select: NM_001142800
dbSNP: rs150140204
Type: single nucleotide variant
Location: chr6:65494695 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Residue 239: the egf-like 2 domain

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

EYS p.Ala239Thr Uncertain significance ★ ⚠ same residue
EYS c.1056+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.1766+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.2259+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3164+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3243+1G>A Pathogenic/Likely pathogenic ★★ same condition
EYS c.3443+1G>T Pathogenic/Likely pathogenic ★★ same condition
EYS c.5928-2A>G Pathogenic ★★ 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-ala239val (accessed [today's date]).

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