Is AIPL1 p.Asp138= (c.414C>T) pathogenic?

AIPL1 p.Asp138= (c.414C>T) is classified Conflicting classifications of pathogenicity in AIPL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-03). Ultra-rare (popmax 0.0134%, eas); Associated with retinitis pigmentosa.

What condition is associated with AIPL1 p.Asp138= (c.414C>T)?

AIPL1 p.Asp138= (c.414C>T) is associated with retinitis pigmentosa, Leber congenital amaurosis 4 (ClinVar).

How common is AIPL1 p.Asp138= (c.414C>T) in the general population?

AIPL1 p.Asp138= (c.414C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

AIPL1 p.Asp138=

c.414C>T · rs565896898 · VCV324618

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

retinitis pigmentosa

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 -5	GERP -4.2
Overall
CADD	1.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,876 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00471% 76/1,612,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
African / African-American	0.00666%	15,010
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.00483%	20,702
Finnishnot grpmax-eligible	0.00323%	30,987
Admixed American	0.00167%	60,022
South Asian	0.0011%	91,090

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.Asp138=
Coding: c.414C>T
MANE Select: NM_014336
dbSNP: rs565896898
Type: single nucleotide variant
Location: chr17:6428369 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 138: the ppiase fkbp-type domain; an α-helix

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis 4

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

AIPL1 p.Asp138His 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
AIPL1 p.Asp51Gly Likely pathogenic ★★★ same condition
AIPL1 p.Cys239Arg 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-asp138 (accessed [today's date]).

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