Is LCA5 p.Pro493fs (c.1476dup) pathogenic?

LCA5 p.Pro493fs (c.1476dup) is classified Pathogenic in LCA5 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2007-07-01). No gnomAD frequency available for this variant; Associated with Leber congenital amaurosis 5.

What condition is associated with LCA5 p.Pro493fs (c.1476dup)?

LCA5 p.Pro493fs (c.1476dup) is associated with Leber congenital amaurosis 5 (ClinVar).

How common is LCA5 p.Pro493fs (c.1476dup) in the general population?

LCA5 p.Pro493fs (c.1476dup) is no gnomAD frequency available for this variant (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.Pro493fs

c.1476dup · rs386834253 · VCV967

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Leber congenital amaurosis 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LCA5
Protein: p.Pro493fs
Coding: c.1476dup
MANE Select: NM_001122769
dbSNP: rs386834253
Type: Duplication
Location: chr6:79487621 (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 p.Asn318fs Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Asn50fs Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Glu457fs Pathogenic ★★ same condition
LCA5 p.Leu577fs Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Thr192fs Pathogenic/Likely pathogenic ★★ same condition
LCA5 p.Ala44fs Likely pathogenic ★ same condition
LCA5 p.Gln479fs Likely pathogenic ★ same condition
LCA5 p.Phe579fs 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/lca5-p-pro493fs (accessed [today's date]).

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