Is AIPL1 p.Arg270Ser (c.808C>A) pathogenic?

AIPL1 p.Arg270Ser (c.808C>A) is classified Conflicting classifications of pathogenicity in AIPL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-04-21). AlphaMissense: likely pathogenic (0.995); Very rare (popmax 6.88e-05%); Associated with AIPL1-related disorder.

What condition is associated with AIPL1 p.Arg270Ser (c.808C>A)?

AIPL1 p.Arg270Ser (c.808C>A) is associated with AIPL1-related disorder (ClinVar).

How common is AIPL1 p.Arg270Ser (c.808C>A) in the general population?

AIPL1 p.Arg270Ser (c.808C>A) is very rare (popmax 6.88e-05%) (gnomAD).

What do computational predictors say about AIPL1 p.Arg270Ser (c.808C>A)?

AlphaMissense predicts likely pathogenic (score 0.995) — an in-silico prediction, not a clinical call.

AIPL1 p.Arg270Ser

c.808C>A · VCV4849185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.88e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AIPL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.995	likely pathogenic · top 2% in AIPL1
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -9.71	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.21, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 9,641 bp · p 0.35 · regional, not allelic
Overall
CADD	24.7	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 6.88e-05%

Overall 6.88e-05% 1/1,452,652 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.Arg270Ser
Coding: c.808C>A
MANE Select: NM_014336
Type: single nucleotide variant
Location: chr17:6425807 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42 · 6 PDB
Residue 270: a UniProt-annotated variant site (in lca4); an α-helix

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

Disease context

AIPL1-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AIPL1 p.Arg270His Pathogenic ★★★ same residue
AIPL1 p.Arg270= Likely benign ★★ same residue
AIPL1 p.Glu361Gln Uncertain significance ★★ ⚠ same condition
AIPL1 c.466-2A>G Likely pathogenic ★ same condition
AIPL1 c.643-1G>A Likely pathogenic ★ same condition
AIPL1 p.His18Pro Likely pathogenic ★ same condition
AIPL1 p.Leu287Arg Likely pathogenic ★ same condition
AIPL1 p.Arg105Lys Conflicting classifications of pathogenicity ★ ⚠ 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-arg270ser (accessed [today's date]).

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