Is RAX2 p.Pro107Ser (c.319C>T) pathogenic?

RAX2 p.Pro107Ser (c.319C>T) is classified Conflicting classifications of pathogenicity in RAX2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-04). AlphaMissense: likely benign (0.0881); Ultra-rare (popmax 0.0476%, sas).

How common is RAX2 p.Pro107Ser (c.319C>T) in the general population?

RAX2 p.Pro107Ser (c.319C>T) is ultra-rare (popmax 0.0476%, sas) (gnomAD).

What do computational predictors say about RAX2 p.Pro107Ser (c.319C>T)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

RAX2 p.Pro107Ser

c.319C>T · rs759806695 · VCV1969942

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	8.266	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0476% South Asian · 40/83,956 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0319%

Overall 0.00281% 43/1,530,834 alleles · ultra-rare exomes 41/1,378,654 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0476%	2,099
Remaining individualsnot grpmax-eligible	0.00168%	59,668
European (non-Finnish)	0.000175%	572,285

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.Pro107Ser
Coding: c.319C>T
MANE Select: NM_001319074
dbSNP: rs759806695
Type: single nucleotide variant
Location: chr19:3770857 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72

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

Similar variants

RAX2 p.Pro107Leu Uncertain significance ★★ ⚠ same residue
RAX2 p.Pro107Arg Uncertain significance ★ ⚠ same residue
RAX2 p.Pro107= 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-pro107ser (accessed [today's date]).

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