Is AIPL1 p.Ser31Tyr (c.92C>A) pathogenic?

AIPL1 p.Ser31Tyr (c.92C>A) is classified Uncertain significance in AIPL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.6269); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with AIPL1 p.Ser31Tyr (c.92C>A)?

AIPL1 p.Ser31Tyr (c.92C>A) is associated with Inborn genetic diseases, Leber congenital amaurosis 4 (ClinVar).

How common is AIPL1 p.Ser31Tyr (c.92C>A) in the general population?

AIPL1 p.Ser31Tyr (c.92C>A) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about AIPL1 p.Ser31Tyr (c.92C>A)?

AlphaMissense predicts likely pathogenic (score 0.6269) — an in-silico prediction, not a clinical call.

AIPL1 p.Ser31Tyr

c.92C>A · rs1458100796 · VCV1421312

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6269	likely pathogenic
REVEL	0.466	indeterminate
SaProt	LLR -11.97	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.91, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,641 bp · p 0.35 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,024 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00041% 6/1,461,866 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.Ser31Tyr
Coding: c.92C>A
MANE Select: NM_014336
dbSNP: rs1458100796
Type: single nucleotide variant
Location: chr17:6435013 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Leber congenital amaurosis 4

Similar variants

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
AIPL1 p.Cys89Arg 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-ser31tyr (accessed [today's date]).

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