Is RAX2 p.Arg79Trp (c.235C>T) pathogenic?

RAX2 p.Arg79Trp (c.235C>T) is classified Uncertain significance in RAX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-23). AlphaMissense: likely pathogenic (0.9953); Very rare (popmax 0.00388%, nfe).

How common is RAX2 p.Arg79Trp (c.235C>T) in the general population?

RAX2 p.Arg79Trp (c.235C>T) is very rare (popmax 0.00388%, nfe) (gnomAD).

What do computational predictors say about RAX2 p.Arg79Trp (c.235C>T)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

RAX2 p.Arg79Trp

c.235C>T · rs1294461966 · VCV1519769

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00388%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic · top 5% in RAX2
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -15.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -3.6, phastCons 0.006
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

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 0.00388% European (non-Finnish) · 45/1,161,238 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.00307% 48/1,561,956 alleles · very rare exomes 46/1,409,776 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00388%	25,805
South Asian	0.00231%	43,360
Remaining individualsnot grpmax-eligible	0.00164%	61,084

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.Arg79Trp
Coding: c.235C>T
MANE Select: NM_001319074
dbSNP: rs1294461966
Type: single nucleotide variant
Location: chr19:3770941 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 79: a DNA-binding region

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

Similar variants

RAX2 p.Arg79Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
RAX2 p.Arg79Pro Uncertain significance ★ ⚠ same residue
RAX2 p.Arg79= Likely benign ★ 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

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-arg79trp (accessed [today's date]).

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