Is ARPIN p.Arg55Lys (c.164G>A) pathogenic?

ARPIN p.Arg55Lys (c.164G>A) is classified Uncertain significance in ARPIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0875); Ultra-rare (popmax 0.0217%, amr).

How common is ARPIN p.Arg55Lys (c.164G>A) in the general population?

ARPIN p.Arg55Lys (c.164G>A) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about ARPIN p.Arg55Lys (c.164G>A)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

ARPIN p.Arg55Lys

c.164G>A · VCV4148189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.02	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 0.38	GERP -1.1, phastCons 0.92
Regional constraint	o/e 1.07	unconstrained · MANE · 11 kb · p 0.24 · regional, not allelic
Overall
CADD	12.72	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

Grpmax group 0.0217% Admixed American · 13/60,016 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000889% 13/1,461,826 alleles · ultra-rare

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: ARPIN
Protein: p.Arg55Lys
Coding: c.164G>A
MANE Select: NM_182616
Type: single nucleotide variant
Location: chr15:89910748 (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-arg55lys (accessed [today's date]).

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