Is AIP p.Ala281Val (c.842C>T) pathogenic?

AIP p.Ala281Val (c.842C>T) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). AlphaMissense: likely benign (0.071); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ala281Val (c.842C>T)?

AIP p.Ala281Val (c.842C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ala281Val (c.842C>T) in the general population?

AIP p.Ala281Val (c.842C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Ala281Val (c.842C>T)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

AIP p.Ala281Val

c.842C>T · rs1865894544 · VCV3223628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -2.64	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 4	GERP 0.84, phastCons 0.65
Overall
CADD	17.39	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.Ala281Val
Coding: c.842C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs1865894544
Type: single nucleotide variant
Location: chr11:67490842 (GRCh38)
Structure: AlphaFold pLDDT 70.14 · 81 PDB

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.Ala281= Likely benign ★★ same residue
AIP p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
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-ala281val (accessed [today's date]).

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