Is AIPL1 p.Pro335= (c.1005C>T) pathogenic?

AIPL1 p.Pro335= (c.1005C>T) is classified Likely benign in AIPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-30). Ultra-rare (popmax 0.049%, eas); Associated with Leber congenital amaurosis 4.

What condition is associated with AIPL1 p.Pro335= (c.1005C>T)?

AIPL1 p.Pro335= (c.1005C>T) is associated with Leber congenital amaurosis 4 (ClinVar).

How common is AIPL1 p.Pro335= (c.1005C>T) in the general population?

AIPL1 p.Pro335= (c.1005C>T) is ultra-rare (popmax 0.049%, eas) (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.Pro335=

c.1005C>T · rs201570681 · VCV2068143

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

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 -6.4	GERP -3
Overall
CADD	1.174	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.049% East Asian · 22/44,872 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00174% 28/1,613,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
Admixed American	0.00333%	30,009
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00017%	589,918

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.Pro335=
Coding: c.1005C>T
MANE Select: NM_014336
dbSNP: rs201570681
Type: single nucleotide variant
Location: chr17:6425610 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 335: the 'disordered' region

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.Pro335Leu Uncertain significance ★ ⚠ same residue
AIPL1 p.Pro335His Benign ⚠ 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
AIPL1 p.Asp51Gly 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/aipl1-p-pro335 (accessed [today's date]).

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