Is ARPIN p.Ala115Pro (c.343G>C) pathogenic?

ARPIN p.Ala115Pro (c.343G>C) is classified Uncertain significance in ARPIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.4421); Absent from gnomAD v4.1.

How common is ARPIN p.Ala115Pro (c.343G>C) in the general population?

ARPIN p.Ala115Pro (c.343G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPIN p.Ala115Pro (c.343G>C)?

AlphaMissense predicts ambiguous (score 0.4421) — an in-silico prediction, not a clinical call.

ARPIN p.Ala115Pro

c.343G>C · VCV4643130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4421 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4421	ambiguous
REVEL	0.092	moderately benign-leaning
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.093, phastCons 0.007
Regional constraint	o/e 1.07	unconstrained · MANE · 11 kb · p 0.24 · regional, not allelic
Overall
CADD	18.74	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: ARPIN
Protein: p.Ala115Pro
Coding: c.343G>C
MANE Select: NM_182616
Type: single nucleotide variant
Location: chr15:89903942 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.31 · 2 PDB

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

Similar variants

ARPIN p.Ala115Val Uncertain significance ★ ⚠ same residue
ARPIN p.Ala139Thr Uncertain significance ★ ⚠ same type
ARPIN p.Ala139Val Uncertain significance ★ ⚠ same type
ARPIN p.Ala23Val Uncertain significance ★ ⚠ same type
ARPIN p.Ala27Thr Uncertain significance ★ ⚠ same type
ARPIN p.Ala76Val Uncertain significance ★ ⚠ same type
ARPIN p.Ala87Thr Uncertain significance ★ ⚠ same type
ARPIN p.Arg159Gln Uncertain significance ★ ⚠ same type

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/arpin-p-ala115pro (accessed [today's date]).

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