Is AIPL1 p.Ser101Pro (c.301T>C) pathogenic?

AIPL1 p.Ser101Pro (c.301T>C) is classified Likely pathogenic in AIPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.9925); Very rare (popmax 8.47e-05%, nfe); Associated with Leber congenital amaurosis.

What condition is associated with AIPL1 p.Ser101Pro (c.301T>C)?

AIPL1 p.Ser101Pro (c.301T>C) is associated with Leber congenital amaurosis (ClinVar).

How common is AIPL1 p.Ser101Pro (c.301T>C) in the general population?

AIPL1 p.Ser101Pro (c.301T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Leber congenital amaurosis inherited?

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

What do computational predictors say about AIPL1 p.Ser101Pro (c.301T>C)?

AlphaMissense predicts likely pathogenic (score 0.9925) — an in-silico prediction, not a clinical call.

AIPL1 p.Ser101Pro

c.301T>C · VCV3544488

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9925 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leber congenital amaurosis

Computational evidence

Protein change
AlphaMissense	0.9925	likely pathogenic ✓ concordant with ClinVar · top 2% in AIPL1
REVEL	0.806	moderately pathogenic-leaning
SaProt	LLR -16.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP -1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,641 bp · p 0.35 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very rare

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.Ser101Pro
Coding: c.301T>C
MANE Select: NM_014336
Type: single nucleotide variant
Location: chr17:6428482 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 101: the ppiase fkbp-type domain; an α-helix

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

Disease context

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

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

AIPL1 p.Ala197Pro Pathogenic ★★★ same condition
AIPL1 p.Arg270His Pathogenic ★★★ same condition
AIPL1 p.Cys239Arg Likely pathogenic ★★★ same condition
AIPL1 p.Gln141Ter Pathogenic ★★★ same condition
AIPL1 p.Trp278Ter Pathogenic ★★★ same condition
AIPL1 p.Val71Phe Likely pathogenic ★★★ same condition
AIPL1 p.Arg272Pro Uncertain significance ★★★ ⚠ same condition
AIPL1 p.Arg80Trp Pathogenic/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-ser101pro (accessed [today's date]).

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