Is USH2A p.Val1866= (c.5598T>C) pathogenic?

USH2A p.Val1866= (c.5598T>C) is classified Conflicting classifications of pathogenicity in USH2A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-13). Very rare (popmax 0.00668%, amr); Associated with retinitis pigmentosa 39.

What condition is associated with USH2A p.Val1866= (c.5598T>C)?

USH2A p.Val1866= (c.5598T>C) is associated with retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Val1866= (c.5598T>C) in the general population?

USH2A p.Val1866= (c.5598T>C) is very rare (popmax 0.00668%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

USH2A p.Val1866=

c.5598T>C · rs771810761 · VCV1065789

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Conditions

retinitis pigmentosa 39

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -3.8, phastCons 0.001
Overall
CADD	5.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% Admixed American · 4/59,870 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00161% 26/1,613,570 alleles · very rare exomes 25/1,461,598 · genomes 1/151,972 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00668%	14,968
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.00161%	62,100

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: USH2A
Protein: p.Val1866=
Coding: c.5598T>C
MANE Select: NM_206933
dbSNP: rs771810761
Type: single nucleotide variant
Location: chr1:216073275 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1866: the laminin g-like 2 domain

Full USH2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 39 — 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

USH2A p.Val1866Ala Uncertain significance ★ same residue
USH2A p.Val1866Ile Uncertain significance ★ same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
USH2A c.8559-2A>G Pathogenic ★★★ same condition
USH2A c.8682-9A>G Pathogenic ★★★ same condition
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
USH2A p.Arg4192Cys Likely 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/ush2a-p-val1866 (accessed [today's date]).

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