Is RAX2 p.Arg44Trp (c.130C>T) pathogenic?

RAX2 p.Arg44Trp (c.130C>T) is classified Uncertain significance in RAX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: ambiguous (0.4037); Very rare (popmax 0.00267%, afr).

How common is RAX2 p.Arg44Trp (c.130C>T) in the general population?

RAX2 p.Arg44Trp (c.130C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about RAX2 p.Arg44Trp (c.130C>T)?

AlphaMissense predicts ambiguous (score 0.4037) — an in-silico prediction, not a clinical call.

RAX2 p.Arg44Trp

c.130C>T · rs761987436 · VCV1928384

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4037	ambiguous
REVEL	0.669	pathogenic-leaning
SaProt	LLR -13.43	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -4.1, phastCons 0.19
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.00267% African / African-American · 2/74,926 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000868% 14/1,612,724 alleles · very rare exomes 13/1,460,542 · genomes 1/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,463
Admixed American	0.00167%	59,908
European (non-Finnish)	0.000932%	107,246

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.Arg44Trp
Coding: c.130C>T
MANE Select: NM_001319074
dbSNP: rs761987436
Type: single nucleotide variant
Location: chr19:3771613 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 44: a DNA-binding region

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

Similar variants

RAX2 p.Arg44Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RAX2 p.Arg44Gly 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-arg44trp (accessed [today's date]).

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