Is RAX p.Pro86Gln (c.257C>A) pathogenic?

RAX p.Pro86Gln (c.257C>A) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely benign (0.0609); Very rare (popmax 0.00169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RAX p.Pro86Gln (c.257C>A)?

RAX p.Pro86Gln (c.257C>A) is associated with Inborn genetic diseases (ClinVar).

How common is RAX p.Pro86Gln (c.257C>A) in the general population?

RAX p.Pro86Gln (c.257C>A) is very rare (popmax 0.00169%, nfe) (gnomAD).

What do computational predictors say about RAX p.Pro86Gln (c.257C>A)?

AlphaMissense predicts likely benign (score 0.0609) — an in-silico prediction, not a clinical call.

RAX p.Pro86Gln

c.257C>A · rs1424241563 · VCV2470152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0609 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0609	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.68	GERP -1, phastCons 0.14
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	8.426	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 19/1,123,750 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000871%

Overall 0.00137% 20/1,464,366 alleles · very rare exomes 18/1,312,268 · genomes 2/152,098 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00177%	56,486
European (non-Finnish)grpmax	0.00169%	59,145

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro86Gln
Coding: c.257C>A
MANE Select: NM_013435
dbSNP: rs1424241563
Type: single nucleotide variant
Location: chr18:59272950 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 86: 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.Pro86Thr Uncertain significance ★ ⚠ same residue
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

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-pro86gln (accessed [today's date]).

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