Is RAX p.Pro280Thr (c.838C>A) pathogenic?

RAX p.Pro280Thr (c.838C>A) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.00559%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RAX p.Pro280Thr (c.838C>A)?

RAX p.Pro280Thr (c.838C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAX p.Pro280Thr (c.838C>A) in the general population?

RAX p.Pro280Thr (c.838C>A) is very rare (popmax 0.00559%, nfe) (gnomAD).

What do computational predictors say about RAX p.Pro280Thr (c.838C>A)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

RAX p.Pro280Thr

c.838C>A · rs368382344 · VCV3152014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -11.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.54, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	19.66	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 0.00559% European (non-Finnish) · 64/1,145,178 alleles

Filtering AF 0.00448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00408%

Overall 0.00437% 67/1,534,154 alleles · very rare exomes 63/1,382,176 · genomes 4/151,978 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00559%	17,893
African / African-American	0.00279%	35,856
Remaining individualsnot grpmax-eligible	0.00168%	59,600

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.Pro280Thr
Coding: c.838C>A
MANE Select: NM_013435
dbSNP: rs368382344
Type: single nucleotide variant
Location: chr18:59269207 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 280: the 'disordered' region

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-pro280thr (accessed [today's date]).

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