Is RAX2 p.Val71Met (c.211G>A) pathogenic?

RAX2 p.Val71Met (c.211G>A) is classified Uncertain significance in RAX2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-21). AlphaMissense: likely pathogenic (0.9922); Ultra-rare (popmax 0.016%, afr).

How common is RAX2 p.Val71Met (c.211G>A) in the general population?

RAX2 p.Val71Met (c.211G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about RAX2 p.Val71Met (c.211G>A)?

AlphaMissense predicts likely pathogenic (score 0.9922) — an in-silico prediction, not a clinical call.

RAX2 p.Val71Met

c.211G>A · rs772852323 · VCV948288

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9922 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9922	likely pathogenic · top 8% in RAX2
REVEL	0.744	pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 0.9, phastCons 0.92
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	24.5	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 0.016% African / African-American · 12/74,774 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00176% 28/1,594,528 alleles · ultra-rare exomes 18/1,442,362 · genomes 10/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,231
Remaining individualsnot grpmax-eligible	0.00485%	20,605
South Asian	0.00113%	88,474
European (non-Finnish)	0.00103%	97,542

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.Val71Met
Coding: c.211G>A
MANE Select: NM_001319074
dbSNP: rs772852323
Type: single nucleotide variant
Location: chr19:3771532 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 71: a DNA-binding region

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

Similar variants

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
RAX2 p.Ala164Val Uncertain significance ★★ ⚠ same type
RAX2 p.Ala180Pro 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-val71met (accessed [today's date]).

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