Is RAX2 p.Ser49Pro (c.145T>C) pathogenic?

RAX2 p.Ser49Pro (c.145T>C) is classified Pathogenic in RAX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely pathogenic (0.9938); Very rare (popmax 8.48e-05%, nfe); Associated with retinitis pigmentosa 95.

What condition is associated with RAX2 p.Ser49Pro (c.145T>C)?

RAX2 p.Ser49Pro (c.145T>C) is associated with retinitis pigmentosa 95 (ClinVar).

How common is RAX2 p.Ser49Pro (c.145T>C) in the general population?

RAX2 p.Ser49Pro (c.145T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RAX2 p.Ser49Pro (c.145T>C)?

AlphaMissense predicts likely pathogenic (score 0.9938) — an in-silico prediction, not a clinical call.

RAX2 p.Ser49Pro

c.145T>C · rs2037262817 · VCV1712267

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 95

Computational evidence

Protein change
AlphaMissense	0.9938	likely pathogenic ✓ concordant with ClinVar · top 7% in RAX2
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -14.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.076, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	24.6	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 8.48e-05% European (non-Finnish) · 1/1,179,526 alleles

Overall 6.2e-05% 1/1,612,192 alleles · very rare exomes 1/1,459,962 · genomes 0/152,230 · joint denominator

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.Ser49Pro
Coding: c.145T>C
MANE Select: NM_001319074
dbSNP: rs2037262817
Type: single nucleotide variant
Location: chr19:3771598 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 49: a DNA-binding region; a UniProt-annotated variant site (in rp95; uncertain significance)

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

Disease context

retinitis pigmentosa 95 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

RAX2 p.Ser49= Likely benign ★ same residue
RAX2 p.Arg57Cys Uncertain significance ★★ ⚠ same condition
RAX2 p.Pro52Leu Benign ★★ same condition
RAX2 p.Arg179Ser Uncertain significance ★ ⚠ same condition
RAX2 p.Arg31Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
RAX2 p.His50Tyr Conflicting classifications of pathogenicity ★ ⚠ same condition
RAX2 p.Ala113fs Uncertain significance ★★ same condition
RAX2 p.Pro52Arg Likely pathogenic ★★ 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-ser49pro (accessed [today's date]).

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