Is AIP p.Arg271Gln (c.812G>A) pathogenic?

AIP p.Arg271Gln (c.812G>A) is classified Uncertain significance in AIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-16). AlphaMissense: likely pathogenic (0.8686); Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg271Gln (c.812G>A)?

AIP p.Arg271Gln (c.812G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg271Gln (c.812G>A) in the general population?

AIP p.Arg271Gln (c.812G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about AIP p.Arg271Gln (c.812G>A)?

AlphaMissense predicts likely pathogenic (score 0.8686) — an in-silico prediction, not a clinical call.

AIP p.Arg271Gln

c.812G>A · rs1448828883 · VCV827469

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8686 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8686	likely pathogenic
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -11.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	33.0	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 0.00133% African / African-American · 1/75,044 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,612,518 alleles · very rare exomes 10/1,460,166 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,044
European (non-Finnish)	0.000763%	131,109

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: AIP
Protein: p.Arg271Gln
Coding: c.812G>A
MANE Select: NM_003977
dbSNP: rs1448828883
Type: single nucleotide variant
Location: chr11:67490812 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 271: a UniProt-annotated variant site (in pita1; uncertain significance); an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same residue
AIP p.Arg271= Likely benign ★ same residue
AIP p.Arg304Ter Pathogenic ★★ same condition
AIP p.Arg81Ter Pathogenic ★★ same condition
AIP p.Cys238Tyr Likely pathogenic ★★ same condition
AIP p.Gln126Ter Pathogenic ★★ same condition
AIP p.Gln14Ter Pathogenic ★★ same condition
AIP p.Gln217Ter 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/aip-p-arg271gln (accessed [today's date]).

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