Is AIP p.Ala274Val (c.821C>T) pathogenic?

AIP p.Ala274Val (c.821C>T) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-23). AlphaMissense: likely pathogenic (0.9453); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ala274Val (c.821C>T)?

AIP p.Ala274Val (c.821C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ala274Val (c.821C>T) in the general population?

AIP p.Ala274Val (c.821C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Ala274Val (c.821C>T)?

AlphaMissense predicts likely pathogenic (score 0.9453) — an in-silico prediction, not a clinical call.

AIP p.Ala274Val

c.821C>T · rs2495409719 · VCV1762506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9453 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9453	likely pathogenic · top 3% in AIP
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -14.85	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 7.6	GERP 2, phastCons 1
Overall
CADD	29.3	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

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.Ala274Val
Coding: c.821C>T
MANE Select: NM_017900 · reported on NM_003977
dbSNP: rs2495409719
Type: single nucleotide variant
Location: chr11:67490821 (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.Ala274Thr Uncertain significance ★★ ⚠ same residue
AIP p.Ala274= Conflicting classifications of pathogenicity ★ same residue
AIP p.Ala274Ser Uncertain significance ★ ⚠ 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

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-ala274val (accessed [today's date]).

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