Is LCA5 p.Glu360= (c.1080A>G) pathogenic?

LCA5 p.Glu360= (c.1080A>G) is classified Conflicting classifications of pathogenicity in LCA5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-03-09). Ultra-rare (popmax 0.0121%, sas); Associated with Leber congenital amaurosis 5.

What condition is associated with LCA5 p.Glu360= (c.1080A>G)?

LCA5 p.Glu360= (c.1080A>G) is associated with Leber congenital amaurosis 5 (ClinVar).

How common is LCA5 p.Glu360= (c.1080A>G) in the general population?

LCA5 p.Glu360= (c.1080A>G) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

How is Leber congenital amaurosis inherited?

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

LCA5 p.Glu360=

c.1080A>G · rs779447463 · VCV358100

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

Leber congenital amaurosis 5

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 -2.2	GERP -3.9
Overall
CADD	0.707	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,070 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000682% 11/1,613,100 alleles · ultra-rare exomes 11/1,460,854 · genomes 0/152,246 · 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: LCA5
Protein: p.Glu360=
Coding: c.1080A>G
MANE Select: NM_001122769
dbSNP: rs779447463
Type: single nucleotide variant
Location: chr6:79491606 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.05

Full LCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 5 — 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

LCA5 c.190+1G>A Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.721-1G>A Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.721-2A>T Pathogenic/Likely pathogenic ★★ same condition
LCA5 c.858+1G>C Likely pathogenic ★★ same condition
LCA5 p.Ala319Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
LCA5 p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Arg255Ter Pathogenic ★★ same condition
LCA5 p.Arg280Ter 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/lca5-p-glu360 (accessed [today's date]).

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