Is AIP p.Arg9Gly (c.25C>G) pathogenic?

AIP p.Arg9Gly (c.25C>G) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: likely benign (0.1257); Absent from gnomAD v4.1.

How common is AIP p.Arg9Gly (c.25C>G) in the general population?

AIP p.Arg9Gly (c.25C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Arg9Gly (c.25C>G)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

AIP p.Arg9Gly

c.25C>G · VCV4741518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AIP
Protein: p.Arg9Gly
Coding: c.25C>G
MANE Select: NM_017900 · reported on NM_003977
Type: single nucleotide variant
Location: chr11:67483183 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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

Similar variants

AIP p.Arg9Trp Uncertain significance ★★ ⚠ same residue
AIP p.Arg9Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AIP p.Arg9Leu Uncertain significance ★ ⚠ same residue
AIP p.Arg9= Likely benign ★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same type
AIP p.Arg304Ter Pathogenic ★★ same type
AIP p.Arg81Ter Pathogenic ★★ same type
AIP p.Cys238Tyr Likely pathogenic ★★ same type

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/aip-p-arg9gly (accessed [today's date]).

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