Is ARPIN p.Thr112Pro (c.334A>C) pathogenic?

ARPIN p.Thr112Pro (c.334A>C) is classified Uncertain significance in ARPIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.1273); Absent from gnomAD v4.1.

How common is ARPIN p.Thr112Pro (c.334A>C) in the general population?

ARPIN p.Thr112Pro (c.334A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPIN p.Thr112Pro (c.334A>C)?

AlphaMissense predicts likely benign (score 0.1273) — an in-silico prediction, not a clinical call.

ARPIN p.Thr112Pro

c.334A>C · VCV4643125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1273 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1273	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -5.52	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 1.2	GERP 0.28, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 11 kb · p 0.24 · regional, not allelic
Overall
CADD	17.06	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: ARPIN
Protein: p.Thr112Pro
Coding: c.334A>C
MANE Select: NM_182616
Type: single nucleotide variant
Location: chr15:89903951 (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.Ala115Pro Uncertain significance ★ ⚠ same type
ARPIN p.Ala115Val Uncertain significance ★ ⚠ same type
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

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-thr112pro (accessed [today's date]).

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