Is RAX p.Pro307= (c.921C>G) pathogenic?

RAX p.Pro307= (c.921C>G) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00664%, sas); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Pro307= (c.921C>G)?

RAX p.Pro307= (c.921C>G) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Pro307= (c.921C>G) in the general population?

RAX p.Pro307= (c.921C>G) is very rare (popmax 0.00664%, sas) (gnomAD).

RAX p.Pro307=

c.921C>G · rs775263241 · VCV891346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00664%, 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 -8.8	GERP -3.5
Overall
CADD	2.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00664% South Asian · 6/90,312 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000373% 6/1,606,654 alleles · very rare exomes 6/1,454,322 · genomes 0/152,332 · 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.Pro307=
Coding: c.921C>G
MANE Select: NM_013435
dbSNP: rs775263241
Type: single nucleotide variant
Location: chr18:59269124 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 307: 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-pro307 (accessed [today's date]).

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