Is AIPL1 p.His260fs (c.778dup) pathogenic?

AIPL1 p.His260fs (c.778dup) is classified Pathogenic in AIPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-18). Absent from gnomAD; Associated with Leber congenital amaurosis 4.

What condition is associated with AIPL1 p.His260fs (c.778dup)?

AIPL1 p.His260fs (c.778dup) is associated with Leber congenital amaurosis 4 (ClinVar).

How common is AIPL1 p.His260fs (c.778dup) in the general population?

AIPL1 p.His260fs (c.778dup) is absent from gnomAD (gnomAD).

How is Cone rod dystrophy inherited?

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

AIPL1 p.His260fs

c.778dup · rs2543883456 · VCV2013018

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Leber congenital amaurosis 4

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 within the last 50 nt of the penultimate exon (5 of 6, 5 nt from its 3' end) — 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	GERP 2.2, 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: AIPL1
Protein: p.His260fs
Coding: c.778dup
MANE Select: NM_014336
dbSNP: rs2543883456
Type: Duplication
Location: chr17:6426620 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB

Full AIPL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leber congenital amaurosis 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

AIPL1 p.His260= Conflicting classifications of pathogenicity ★ same residue
AIPL1 p.Val12fs Likely pathogenic ★★★ same condition
AIPL1 p.Ala352_Pro355dup Uncertain significance ★★★ same condition
AIPL1 p.Glu318fs Pathogenic/Likely pathogenic ★★ same condition
AIPL1 p.Lys200fs Pathogenic ★★ same condition
AIPL1 p.Phe35delinsLeuTer Pathogenic ★★ same condition
AIPL1 p.Asn171fs Pathogenic ★ same condition
AIPL1 p.His60fs 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/aipl1-p-his260fs (accessed [today's date]).

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