Is RD3 p.Val84= (c.252C>T) pathogenic?

RD3 p.Val84= (c.252C>T) is classified Likely benign in RD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0208%, nfe); Associated with Leber congenital amaurosis 12.

What condition is associated with RD3 p.Val84= (c.252C>T)?

RD3 p.Val84= (c.252C>T) is associated with Leber congenital amaurosis 12 (ClinVar).

How common is RD3 p.Val84= (c.252C>T) in the general population?

RD3 p.Val84= (c.252C>T) is ultra-rare (popmax 0.0208%, nfe) (gnomAD).

How is Leber congenital amaurosis inherited?

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

RD3 p.Val84=

c.252C>T · rs758095282 · VCV1091404

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, nfe)

Conditions

Leber congenital amaurosis 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.48	GERP -4, phastCons 0.005
Overall
CADD	1.386	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% European (non-Finnish) · 245/1,180,054 alleles

Filtering AF 0.0186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.0156% 252/1,614,162 alleles · ultra-rare exomes 242/1,461,886 · genomes 10/152,276 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0208%	4,817
Remaining individualsnot grpmax-eligible	0.0048%	20,830
African / African-American	0.004%	24,987
Finnishnot grpmax-eligible	0.00156%	64,044

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: RD3
Protein: p.Val84=
Coding: c.252C>T
MANE Select: NM_001164688
dbSNP: rs758095282
Type: single nucleotide variant
Location: chr1:211481164 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB
Residue 84: an α-helix

Full RD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 12 — 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

RD3 c.296+1G>T Pathogenic/Likely pathogenic ★★ same condition
RD3 p.Arg38Ter Pathogenic ★★ same condition
RD3 p.Tyr60Ter Pathogenic ★★ same condition
RD3 c.-572G>A Uncertain significance ★★ same condition
RD3 c.*1277G>A Uncertain significance ★★ same condition
RD3 p.Ala135Val Uncertain significance ★★ ⚠ same condition
RD3 p.Arg15Trp Uncertain significance ★★ ⚠ same condition
RD3 p.Arg182Gln Uncertain significance ★★ ⚠ 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/rd3-p-val84 (accessed [today's date]).

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