Is RD3 p.Leu79= (c.235T>C) pathogenic?

RD3 p.Leu79= (c.235T>C) is classified Benign in RD3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Low-frequency (popmax 2.85%, afr); Associated with Leber congenital amaurosis 12.

What condition is associated with RD3 p.Leu79= (c.235T>C)?

RD3 p.Leu79= (c.235T>C) is associated with Leber congenital amaurosis 12 (ClinVar).

How common is RD3 p.Leu79= (c.235T>C) in the general population?

RD3 p.Leu79= (c.235T>C) is low-frequency (popmax 2.85%, afr) (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.Leu79=

c.235T>C · rs35937732 · VCV707693

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, afr)

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 6.6	GERP -0.12, phastCons 1
Overall
CADD	3.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.85% African / African-American · 2,141/75,078 alleles

Filtering AF 2.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.71%

Overall 0.157% 2,541/1,614,278 alleles · low-frequency exomes 1,299/1,461,888 · genomes 1,242/152,390 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.85%	35
Middle Eastern	0.429%	233
Remaining individualsnot grpmax-eligible	0.24%	417
Admixed American	0.215%	465
South Asian	0.0198%	5,060
European (non-Finnish)	0.00644%	15,527
Finnishnot grpmax-eligible	0.00156%	64,046

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.Leu79=
Coding: c.235T>C
MANE Select: NM_001164688
dbSNP: rs35937732
Type: single nucleotide variant
Location: chr1:211481181 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 1 PDB
Residue 79: 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-leu79 (accessed [today's date]).

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