Is RAX2 p.Met1Val (c.1A>G) pathogenic?

RAX2 p.Met1Val (c.1A>G) is classified Pathogenic in RAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). Very rare (popmax 0.00401%, afr).

How common is RAX2 p.Met1Val (c.1A>G) in the general population?

RAX2 p.Met1Val (c.1A>G) is very rare (popmax 0.00401%, afr) (gnomAD).

RAX2 p.Met1Val

c.1A>G · VCV4779831

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.63	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.5, phastCons 1
Overall
CADD	13.05	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,850 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000375% 6/1,597,874 alleles · very rare exomes 4/1,445,742 · genomes 2/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,950
South Asian	0.00223%	44,914
Remaining individualsnot grpmax-eligible	0.00161%	62,072

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001319074
Type: single nucleotide variant
Location: chr19:3771742 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 1: the 'disordered' 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-met1val (accessed [today's date]).

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