Is AIP p.Ser131Arg (c.391A>C) pathogenic?

AIP p.Ser131Arg (c.391A>C) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-29). AlphaMissense: ambiguous (0.3851); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Ser131Arg (c.391A>C)?

AIP p.Ser131Arg (c.391A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Ser131Arg (c.391A>C) in the general population?

AIP p.Ser131Arg (c.391A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AIP p.Ser131Arg (c.391A>C)?

AlphaMissense predicts ambiguous (score 0.3851) — an in-silico prediction, not a clinical call.

AIP p.Ser131Arg

c.391A>C · VCV4868514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3851	ambiguous
REVEL	0.173	moderately benign-leaning
SaProt	LLR -7.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.3, phastCons 0.68
Overall
CADD	19.31	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.Ser131Arg
Coding: c.391A>C
MANE Select: NM_003977
Type: single nucleotide variant
Location: chr11:67489378 (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

Disease context

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

Similar variants

AIP p.Ser131Gly Uncertain significance ★★ ⚠ same residue
AIP p.Ser131= 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

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-ser131arg (accessed [today's date]).

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