Is RAX p.Pro89fs (c.266del) pathogenic?

RAX p.Pro89fs (c.266del) is classified Pathogenic in RAX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-09). Very rare (popmax 0.00294%, sas); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Pro89fs (c.266del)?

RAX p.Pro89fs (c.266del) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Pro89fs (c.266del) in the general population?

RAX p.Pro89fs (c.266del) is very rare (popmax 0.00294%, sas) (gnomAD).

RAX p.Pro89fs

c.266del · rs2511488658 · VCV1723190

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00294%, sas)

Conditions

isolated microphthalmia 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.5	GERP -3.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00294% South Asian · 2/68,002 alleles

Filtering AF 0.000488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000183%

Overall 0.000137% 2/1,457,946 alleles · very rare exomes 2/1,305,802 · genomes 0/152,144 · 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: RAX
Protein: p.Pro89fs
Coding: c.266del
MANE Select: NM_013435
dbSNP: rs2511488658
Type: Deletion
Location: chr18:59272941 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 89: the 'disordered' region

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

Disease context

isolated microphthalmia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAX c.*1300A>G Uncertain significance ★★ same condition
RAX c.*850C>T Uncertain significance ★★ same condition
RAX p.Ala267Val Uncertain significance ★★ ⚠ same condition
RAX p.Ala72Gly Uncertain significance ★★ ⚠ same condition
RAX p.Arg110Gly Uncertain significance ★★ ⚠ same condition
RAX p.Arg166Pro Uncertain significance ★★ ⚠ same condition
RAX p.Glu96Gln Uncertain significance ★★ ⚠ same condition
RAX p.Gly237Asp 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-pro89fs (accessed [today's date]).

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