Is RAX2 p.Pro140= (c.420G>A) pathogenic?

RAX2 p.Pro140= (c.420G>A) is classified Likely benign in RAX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-22). Very rare (popmax 0.00358%, sas).

How common is RAX2 p.Pro140= (c.420G>A) in the general population?

RAX2 p.Pro140= (c.420G>A) is very rare (popmax 0.00358%, sas) (gnomAD).

RAX2 p.Pro140=

c.420G>A · rs947549671 · VCV1384637

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00358%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.018	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3
Overall
CADD	0.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00358% South Asian · 3/83,800 alleles

Filtering AF 0.000951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00074%

Overall 0.00137% 21/1,529,818 alleles · very rare exomes 19/1,377,630 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00358%	27,933
European (non-Finnish)	0.00149%	67,304
African / African-American	0.00139%	72,060

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.Pro140=
Coding: c.420G>A
MANE Select: NM_001319074
dbSNP: rs947549671
Type: single nucleotide variant
Location: chr19:3770756 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 140: a UniProt-annotated variant site (in cord11; uncertain significance; decreased interaction with crx and increased transactivation activity)

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

Similar variants

RAX2 p.Pro140Arg Uncertain significance ★ ⚠ same residue
RAX2 p.Pro140Leu 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-pro140 (accessed [today's date]).

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