Is RAX p.Pro342Gln (c.1025C>A) pathogenic?

RAX p.Pro342Gln (c.1025C>A) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.3818); Very rare (popmax 0.00533%, afr); Associated with Inborn genetic diseases.

What condition is associated with RAX p.Pro342Gln (c.1025C>A)?

RAX p.Pro342Gln (c.1025C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAX p.Pro342Gln (c.1025C>A) in the general population?

RAX p.Pro342Gln (c.1025C>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about RAX p.Pro342Gln (c.1025C>A)?

AlphaMissense predicts ambiguous (score 0.3818) — an in-silico prediction, not a clinical call.

RAX p.Pro342Gln

c.1025C>A · VCV4151146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3818 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3818	ambiguous
REVEL	0.534	indeterminate
SaProt	LLR -9.57	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	32.0	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 0.00533% African / African-American · 4/75,060 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,613,058 alleles · very rare exomes 3/1,460,702 · genomes 2/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,765
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: RAX
Protein: p.Pro342Gln
Coding: c.1025C>A
MANE Select: NM_013435
Type: single nucleotide variant
Location: chr18:59269020 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAX p.Ala267Val Uncertain significance ★★ ⚠ same condition
RAX p.Ala72Gly Uncertain significance ★★ ⚠ same condition
RAX p.Arg166Pro Uncertain significance ★★ ⚠ same condition
RAX p.Glu96Gln Uncertain significance ★★ ⚠ same condition
RAX p.Leu289Phe Uncertain significance ★★ ⚠ same condition
RAX p.Lys333Arg Uncertain significance ★★ ⚠ same condition
RAX p.Phe51Leu Uncertain significance ★★ ⚠ same condition
RAX p.Pro279Ala Uncertain significance ★★ ⚠ same condition

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/rax-p-pro342gln (accessed [today's date]).

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