Is AIPL1 p.Cys89= (c.267C>T) pathogenic?

AIPL1 p.Cys89= (c.267C>T) is classified Conflicting classifications of pathogenicity in AIPL1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.563%, nfe); Associated with Leber congenital amaurosis 4.

What condition is associated with AIPL1 p.Cys89= (c.267C>T)?

AIPL1 p.Cys89= (c.267C>T) is associated with Leber congenital amaurosis 4, inherited retinal dystrophy (ClinVar).

How common is AIPL1 p.Cys89= (c.267C>T) in the general population?

AIPL1 p.Cys89= (c.267C>T) is rare (popmax 0.563%, 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.Cys89=

c.267C>T · rs62653020 · VCV95582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.563%, 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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.4	GERP -3.5
Overall
CADD	1.576	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.563% European (non-Finnish) · 6,640/1,179,906 alleles

Filtering AF 0.551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.547%

Overall 0.493% 7,962/1,613,722 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.31%	76
European (non-Finnish)grpmax	0.563%	178
Finnishnot grpmax-eligible	0.55%	182
Remaining individualsnot grpmax-eligible	0.527%	190
Admixed American	0.17%	588
Middle Eastern	0.117%	853
African / African-American	0.088%	1,137
South Asian	0.078%	1,281
East Asian	0.0178%	5,606

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.Cys89=
Coding: c.267C>T
MANE Select: NM_014336
dbSNP: rs62653020
Type: single nucleotide variant
Location: chr17:6433928 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 89: the ppiase fkbp-type domain; a β-strand

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

Also linked: inherited retinal dystrophy

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.Cys89Arg Pathogenic ★★★ same residue
AIPL1 p.Cys89Ter Pathogenic ★ 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-cys89 (accessed [today's date]).

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