AIPL1 p.Phe37=
c.111C>T · rs11650007 · VCV99789
ClinGen expert panel — Leber Congenital Amaurosis/early onset Retinal Dystrophy VCEP
Benign for AIPL1-related retinopathy. Applied ACMG criteria (verbatim):
BS2 BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
NM_014336.5(AIPL1):c.111C>T (p.Phe37=) is a synonymous variant in exon 2 of 6. The change from C to T at c.111 is not predicted to change the amino acid phenylalanine at position p.37. This variant is present in gnomAD v.4.1.0 at a Grpmax allele frequency of 0.03109, with 37005 alleles / 1,179,952 total alleles in the European (non-Finnish) population, which is higher than the ClinGen LCA/eoRD VCEP BA1 threshold of >0.0057 (BA1). Additionally, the variant has been found in the homozygous state in 748 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of ≥6 (gnomAD version 4.1.0; BS2). The splicing impact predictor SpliceAI gives a delta score of 0.08, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4, BP7). In summary, this variant meets the criteria to be classified as Benign for AIPL1-related retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP: BA1, BS2, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/24/2025).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 2.6 | GERP -0.4, phastCons 1 |
| Overall | ||
| CADD | 6.698 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 4.99% | 20 |
| Amishnot grpmax-eligible | 3.96% | 25 |
| European (non-Finnish)grpmax | 3.14% | 32 |
| Remaining individualsnot grpmax-eligible | 1.73% | 58 |
| Admixed American | 0.552% | 181 |
| African / African-American | 0.477% | 209 |
| Middle Eastern | 0.396% | 252 |
| Ashkenazi Jewishnot grpmax-eligible | 0.382% | 262 |
| South Asian | 0.103% | 969 |
Finnish 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.Phe37=
- Coding
- c.111C>T
- MANE Select
- NM_014336
- dbSNP
- rs11650007
- Type
- single nucleotide variant
- Location
- chr17:6434084 (GRCh38)
- Gene constraint
- LOEUF 1.01 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.42 · 6 PDB
- Residue 37
- a β-strand
Similar variants
- AIPL1 c.276+1G>A Pathogenic ★★★ same condition
- AIPL1 c.276+2T>C 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-phe37 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown