Is RAX p.Leu39= (c.117G>A) pathogenic?

RAX p.Leu39= (c.117G>A) is classified Likely benign in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Ultra-rare (popmax 0.0488%, sas); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Leu39= (c.117G>A)?

RAX p.Leu39= (c.117G>A) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Leu39= (c.117G>A) in the general population?

RAX p.Leu39= (c.117G>A) is ultra-rare (popmax 0.0488%, sas) (gnomAD).

RAX p.Leu39=

c.117G>A · VCV4745641

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0488%, 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 2.6	GERP 1.8, phastCons 1
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0488% South Asian · 41/84,048 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.00306% 47/1,535,148 alleles · ultra-rare exomes 38/1,382,826 · genomes 9/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0488%	2,050
Ashkenazi Jewishnot grpmax-eligible	0.00699%	14,309
Remaining individualsnot grpmax-eligible	0.00667%	14,992

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.Leu39=
Coding: c.117G>A
MANE Select: NM_013435
Type: single nucleotide variant
Location: chr18:59273090 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10

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-leu39 (accessed [today's date]).

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