Is RDH12 p.Arg249= (c.745C>A) pathogenic?

RDH12 p.Arg249= (c.745C>A) is classified Likely benign in RDH12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). Very rare (popmax 0.0011%, sas); Associated with Leber congenital amaurosis 13.

What condition is associated with RDH12 p.Arg249= (c.745C>A)?

RDH12 p.Arg249= (c.745C>A) is associated with Leber congenital amaurosis 13 (ClinVar).

How common is RDH12 p.Arg249= (c.745C>A) in the general population?

RDH12 p.Arg249= (c.745C>A) is very rare (popmax 0.0011%, sas) (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.Arg249=

c.745C>A · rs1452061026 · VCV1111889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Leber congenital amaurosis 13

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 -0.35	GERP -4.8, phastCons 0.036
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000187% 3/1,605,996 alleles · very rare exomes 3/1,453,674 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,008
European (non-Finnish)	0.000169%	589,977

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.Arg249=
Coding: c.745C>A
MANE Select: NM_152443
dbSNP: rs1452061026
Type: single nucleotide variant
Location: chr14:67729277 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.21

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)

Similar variants

RDH12 c.68+1G>A Pathogenic ★★ same condition
RDH12 p.Ala206Asp Likely pathogenic ★★ same condition
RDH12 p.Ala47Thr Pathogenic/Likely pathogenic ★★ same condition
RDH12 p.Asn147Thr Likely pathogenic ★★ same condition
RDH12 p.Glu77Ter Pathogenic/Likely pathogenic ★★ same condition
RDH12 p.Leu93Pro Pathogenic/Likely pathogenic ★★ same condition
RDH12 p.Tyr194Ter Pathogenic ★★ same condition
RDH12 p.Tyr200Cys Pathogenic/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/rdh12-p-arg249 (accessed [today's date]).

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