Is AIPL1 p.Pro295= (c.885G>A) pathogenic?

AIPL1 p.Pro295= (c.885G>A) is classified Likely benign in AIPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). Very rare (popmax 8.47e-05%, nfe); Associated with Leber congenital amaurosis 4.

What condition is associated with AIPL1 p.Pro295= (c.885G>A)?

AIPL1 p.Pro295= (c.885G>A) is associated with Leber congenital amaurosis 4 (ClinVar).

How common is AIPL1 p.Pro295= (c.885G>A) in the general population?

AIPL1 p.Pro295= (c.885G>A) is very rare (popmax 8.47e-05%, nfe) (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.Pro295=

c.885G>A · rs1276719586 · VCV2792940

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Leber congenital amaurosis 4

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 -8.2	GERP -4.5
Overall
CADD	5.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,996 alleles

Overall 0.000137% 2/1,455,342 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)grpmax	8.47e-05%	1,179,997

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AIPL1
Protein: p.Pro295=
Coding: c.885G>A
MANE Select: NM_014336
dbSNP: rs1276719586
Type: single nucleotide variant
Location: chr17:6425730 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 295: an α-helix

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.Pro295Arg Uncertain significance ★★ ⚠ same residue
AIPL1 p.Pro295Leu Uncertain significance ★ ⚠ same residue
AIPL1 p.Pro295Gln Uncertain significance ★ ⚠ same residue
AIPL1 c.276+1G>A Pathogenic ★★★ same condition
AIPL1 c.277-2A>G Pathogenic ★★★ same condition
AIPL1 p.Ala197Pro Pathogenic ★★★ same condition
AIPL1 p.Arg270His Pathogenic ★★★ same condition
AIPL1 p.Arg32Ter 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-pro295 (accessed [today's date]).

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