Is RDH5 p.Val264= (c.792G>A) pathogenic?

RDH5 p.Val264= (c.792G>A) is classified Conflicting classifications of pathogenicity in RDH5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-03-16). Very rare (popmax 0.00339%, nfe); Associated with fundus albipunctatus.

What condition is associated with RDH5 p.Val264= (c.792G>A)?

RDH5 p.Val264= (c.792G>A) is associated with fundus albipunctatus (ClinVar).

How common is RDH5 p.Val264= (c.792G>A) in the general population?

RDH5 p.Val264= (c.792G>A) is very rare (popmax 0.00339%, nfe) (gnomAD).

How is Fundus albipunctatus inherited?

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

RDH5 p.Val264=

c.792G>A · rs746999951 · VCV882946

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 0.00339%, nfe)

Conditions

fundus albipunctatus

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
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.6	GERP -0.29, phastCons 1
Overall
CADD	13.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,180,046 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00273% 44/1,614,204 alleles · very rare exomes 44/1,461,894 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,501
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00133%	75,028
South Asian	0.0011%	91,084

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: RDH5
Protein: p.Val264=
Coding: c.792G>A
MANE Select: NM_002905
dbSNP: rs746999951
Type: single nucleotide variant
Location: chr12:55724380 (GRCh38)
Gene constraint: LOEUF 1.3 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.02
Residue 264: a UniProt-annotated variant site (in falbi; decreased stability)

Full RDH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

fundus albipunctatus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fundus albipunctatus (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

RDH5 p.Gly238Trp Pathogenic/Likely pathogenic ★★ same condition
RDH5 p.Val203Glu Uncertain significance ★ ⚠ same condition
RDH5 p.Leu24fs Pathogenic ★★ same condition
RDH5 p.Ala26Thr Uncertain significance ★★ ⚠ same type
RDH5 p.Arg191Trp Uncertain significance ★★ ⚠ same type
RDH5 p.Arg251His Uncertain significance ★★ ⚠ same type
RDH5 p.Ser300Ile Uncertain significance ★★ ⚠ same type
RDH5 c.569+54C>T Benign ★★ 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/rdh5-p-val264 (accessed [today's date]).

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