Is RD3 p.Val173= (c.519G>A) pathogenic?

RD3 p.Val173= (c.519G>A) is classified Conflicting classifications of pathogenicity in RD3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-16). Rare (popmax 0.446%, eas); Associated with Leber congenital amaurosis 12.

What condition is associated with RD3 p.Val173= (c.519G>A)?

RD3 p.Val173= (c.519G>A) is associated with Leber congenital amaurosis 12, inherited retinal dystrophy (ClinVar).

How common is RD3 p.Val173= (c.519G>A) in the general population?

RD3 p.Val173= (c.519G>A) is rare (popmax 0.446%, eas) (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.Val173=

c.519G>A · rs139419737 · VCV772783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.446%, eas)

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 3.2	GERP 1.3, phastCons 1
Overall
CADD	12.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.446% East Asian · 200/44,846 alleles

Filtering AF 0.395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.376%

Overall 0.0483% 778/1,611,772 alleles · rare exomes 681/1,459,400 · genomes 97/152,372 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.446%	224
Finnishnot grpmax-eligible	0.417%	240
Remaining individualsnot grpmax-eligible	0.0658%	1,520
European (non-Finnish)	0.0229%	4,369
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,770
South Asian	0.0033%	30,276

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.Val173=
Coding: c.519G>A
MANE Select: NM_001164688
dbSNP: rs139419737
Type: single nucleotide variant
Location: chr1:211479105 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB
Residue 173: the 'disordered' region

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

Also linked: inherited retinal dystrophy

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-val173 (accessed [today's date]).

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