Is RAX2 p.Arg87Pro (c.260G>C) pathogenic?

RAX2 p.Arg87Pro (c.260G>C) is classified Uncertain significance in RAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: likely pathogenic (0.652); Very rare (popmax 0.00188%, amr).

How common is RAX2 p.Arg87Pro (c.260G>C) in the general population?

RAX2 p.Arg87Pro (c.260G>C) is very rare (popmax 0.00188%, amr) (gnomAD).

What do computational predictors say about RAX2 p.Arg87Pro (c.260G>C)?

AlphaMissense predicts likely pathogenic (score 0.652) — an in-silico prediction, not a clinical call.

RAX2 p.Arg87Pro

c.260G>C · rs121908280 · VCV2050516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.652	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -10.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.019	GERP -3.1, phastCons 0.013
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	23.5	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 0.00188% Admixed American · 1/53,238 alleles

Overall 6.42e-05% 1/1,557,286 alleles · very rare exomes 0/1,405,100 · genomes 1/152,186 · joint denominator

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: RAX2
Protein: p.Arg87Pro
Coding: c.260G>C
MANE Select: NM_001319074
dbSNP: rs121908280
Type: single nucleotide variant
Location: chr19:3770916 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 87: a UniProt-annotated variant site (in armd6; uncertain significance; increased transactivation and dna-binding activity)

Full RAX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAX2 p.Arg87Gln Uncertain significance ★★ ⚠ same residue
RAX2 p.Arg87Trp Uncertain significance ★★ ⚠ same residue
RAX2 p.Pro52Arg Likely pathogenic ★★ same type
RAX2 c.217-12C>A Uncertain significance ★★ same type
RAX2 c.*368C>T Uncertain significance ★★ same type
RAX2 p.Ala105Val Uncertain significance ★★ ⚠ same type
RAX2 p.Ala109Thr Uncertain significance ★★ ⚠ same type
RAX2 p.Ala160Val 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/rax2-p-arg87pro (accessed [today's date]).

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