Is AIP p.Pro300Leu (c.899C>T) pathogenic?

AIP p.Pro300Leu (c.899C>T) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-06). AlphaMissense: likely benign (0.1674); Absent from gnomAD v4.1.

How common is AIP p.Pro300Leu (c.899C>T) in the general population?

AIP p.Pro300Leu (c.899C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Pro300Leu (c.899C>T)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

AIP p.Pro300Leu

c.899C>T · rs2134256678 · VCV1318543

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.84, phastCons 1
Overall
CADD	20.3	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

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.Pro300Leu
Coding: c.899C>T
MANE Select: NM_003977
dbSNP: rs2134256678
Type: single nucleotide variant
Location: chr11:67490899 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 300: an α-helix

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

Similar variants

AIP p.Pro300Ser Uncertain significance ★★ ⚠ same residue
AIP p.Pro300= 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
AIP p.Gln126Ter Pathogenic ★★ same type
AIP p.Gln14Ter 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-pro300leu (accessed [today's date]).

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