Is RAX2 p.Ala22= (c.66C>T) pathogenic?

RAX2 p.Ala22= (c.66C>T) is classified Likely benign in RAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). Very rare (popmax 6.2e-05%).

How common is RAX2 p.Ala22= (c.66C>T) in the general population?

RAX2 p.Ala22= (c.66C>T) is very rare (popmax 6.2e-05%) (gnomAD).

RAX2 p.Ala22=

c.66C>T · rs2512318681 · VCV3006706

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.108	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.2, phastCons 0.88
Overall
CADD	9.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,984 alleles · very rare exomes 1/1,460,722 · genomes 0/152,262 · 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.Ala22=
Coding: c.66C>T
MANE Select: NM_001319074
dbSNP: rs2512318681
Type: single nucleotide variant
Location: chr19:3771677 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 22: the 'disordered' region

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

Similar variants

RAX2 p.Ala22Thr 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
RAX2 p.Ala164Val 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-ala22 (accessed [today's date]).

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