Is RAX p.Pro93= (c.279C>A) pathogenic?

RAX p.Pro93= (c.279C>A) is classified Uncertain significance in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0199%, eas); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Pro93= (c.279C>A)?

RAX p.Pro93= (c.279C>A) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Pro93= (c.279C>A) in the general population?

RAX p.Pro93= (c.279C>A) is ultra-rare (popmax 0.0199%, eas) (gnomAD).

RAX p.Pro93=

c.279C>A · rs780219769 · VCV892545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, eas)

Conditions

isolated microphthalmia 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0199% East Asian · 8/40,238 alleles

Filtering AF 0.00981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00714%

Overall 0.000748% 11/1,471,120 alleles · ultra-rare exomes 9/1,318,980 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0199%	5,030
Remaining individualsnot grpmax-eligible	0.00354%	28,267
European (non-Finnish)	8.85e-05%	1,129,442

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.Pro93=
Coding: c.279C>A
MANE Select: NM_013435
dbSNP: rs780219769
Type: single nucleotide variant
Location: chr18:59272928 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 93: 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-pro93 (accessed [today's date]).

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