Is RDH12 p.Arg65= (c.195A>G) pathogenic?

RDH12 p.Arg65= (c.195A>G) is classified Likely benign in RDH12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-19). Very rare (popmax 0.000339%, nfe); Associated with Leber congenital amaurosis 13.

What condition is associated with RDH12 p.Arg65= (c.195A>G)?

RDH12 p.Arg65= (c.195A>G) is associated with Leber congenital amaurosis 13 (ClinVar).

How common is RDH12 p.Arg65= (c.195A>G) in the general population?

RDH12 p.Arg65= (c.195A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Leber congenital amaurosis inherited?

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

RDH12 p.Arg65=

c.195A>G · rs771614823 · VCV1013046

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Leber congenital amaurosis 13

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.49	GERP -4.8
Overall
CADD	6.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,030 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,020 alleles · very rare exomes 3/1,461,892 · genomes 1/152,128 · joint denominator

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: RDH12
Protein: p.Arg65=
Coding: c.195A>G
MANE Select: NM_152443
dbSNP: rs771614823
Type: single nucleotide variant
Location: chr14:67725106 (GRCh38)

Full RDH12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

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/rdh12-p-arg65 (accessed [today's date]).

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