Is AIP p.Pro26Arg (c.77C>G) pathogenic?

AIP p.Pro26Arg (c.77C>G) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.3282); Absent from gnomAD v4.1.

How common is AIP p.Pro26Arg (c.77C>G) in the general population?

AIP p.Pro26Arg (c.77C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Pro26Arg (c.77C>G)?

AlphaMissense predicts likely benign (score 0.3282) — an in-silico prediction, not a clinical call.

AIP p.Pro26Arg

c.77C>G · rs2134247769 · VCV1367273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3282 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3282	likely benign
REVEL	0.708	pathogenic-leaning
SaProt	LLR -12.29	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 1
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

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.Pro26Arg
Coding: c.77C>G
MANE Select: NM_003977
dbSNP: rs2134247769
Type: single nucleotide variant
Location: chr11:67483235 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB

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

Similar variants

AIP p.Pro26Ala Uncertain significance ★★ ⚠ same residue
AIP p.Pro26Leu Uncertain significance ★★ ⚠ same residue
AIP p.Pro26= 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

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-pro26arg (accessed [today's date]).

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