Is RAX p.Pro250= (c.750G>A) pathogenic?

RAX p.Pro250= (c.750G>A) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.005%, sas); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Pro250= (c.750G>A)?

RAX p.Pro250= (c.750G>A) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Pro250= (c.750G>A) in the general population?

RAX p.Pro250= (c.750G>A) is very rare (popmax 0.005%, sas) (gnomAD).

RAX p.Pro250=

c.750G>A · rs1487028248 · VCV891348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, sas)

Conditions

isolated microphthalmia 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.6	GERP -2.7
Overall
CADD	11.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% South Asian · 2/39,974 alleles

Filtering AF 0.000829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00031%

Overall 0.000699% 9/1,287,522 alleles · very rare exomes 6/1,137,004 · genomes 3/150,518 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.005%	19,987
Admixed American	0.00389%	25,734
African / African-American	0.00313%	31,965
European (non-Finnish)	0.000391%	255,806

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.Pro250=
Coding: c.750G>A
MANE Select: NM_013435
dbSNP: rs1487028248
Type: single nucleotide variant
Location: chr18:59269295 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 250: 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-pro250 (accessed [today's date]).

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