Is AIP p.Arg314Pro (c.941G>C) pathogenic?

AIP p.Arg314Pro (c.941G>C) is classified Uncertain significance in AIP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely pathogenic (0.9318); Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with AIP p.Arg314Pro (c.941G>C)?

AIP p.Arg314Pro (c.941G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AIP p.Arg314Pro (c.941G>C) in the general population?

AIP p.Arg314Pro (c.941G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about AIP p.Arg314Pro (c.941G>C)?

AlphaMissense predicts likely pathogenic (score 0.9318) — an in-silico prediction, not a clinical call.

AIP p.Arg314Pro

c.941G>C · rs540000299 · VCV1766900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9318	likely pathogenic
REVEL	0.57	indeterminate
SaProt	LLR -13.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.82, phastCons 1
Overall
CADD	26.9	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 0.0011% South Asian · 1/90,990 alleles

Overall 0.000124% 2/1,612,162 alleles · very rare exomes 2/1,459,822 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,990
European (non-Finnish)	8.48e-05%	1,179,724

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.Arg314Pro
Coding: c.941G>C
MANE Select: NM_003977
dbSNP: rs540000299
Type: single nucleotide variant
Location: chr11:67490941 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 91.09 · 5 PDB
Residue 314: 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.Arg314Gln Uncertain significance ★★ ⚠ same residue
AIP p.Arg314Trp Uncertain significance ★★ ⚠ same residue
AIP p.Arg314Leu 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-arg314pro (accessed [today's date]).

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