Is RAX2 p.138PG[3] (c.411CCCGGG[3]) pathogenic?

RAX2 p.138PG[3] (c.411CCCGGG[3]) is classified Conflicting classifications of pathogenicity in RAX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.428%, sas); Associated with cone-rod dystrophy 11.

What condition is associated with RAX2 p.138PG[3] (c.411CCCGGG[3])?

RAX2 p.138PG[3] (c.411CCCGGG[3]) is associated with cone-rod dystrophy 11 (ClinVar).

How common is RAX2 p.138PG[3] (c.411CCCGGG[3]) in the general population?

RAX2 p.138PG[3] (c.411CCCGGG[3]) is rare (popmax 0.428%, sas) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

RAX2 p.138PG[3]

c.411CCCGGG[3] · rs549932754 · VCV1242

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.428%, sas)

Conditions

cone-rod dystrophy 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.003	GERP -1.8, phastCons 0.093
Overall
CADD	11.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.428% South Asian · 359/83,838 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.377%

Overall 0.032% 490/1,531,106 alleles · rare exomes 468/1,378,794 · genomes 22/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.428%	234
Remaining individualsnot grpmax-eligible	0.0335%	2,984
European (non-Finnish)	0.00952%	10,501
East Asian	0.00247%	40,406
Admixed American	0.00197%	50,760

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: RAX2
Protein: p.138PG[3]
Coding: c.411CCCGGG[3]
MANE Select: NM_001319074
dbSNP: rs549932754
Type: Microsatellite
Location: chr19:3770753 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72

Full RAX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cone-rod dystrophy 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

RAX2 p.Ala156fs Pathogenic/Likely pathogenic ★★ same condition
RAX2 c.*368C>T Uncertain significance ★★ same condition
RAX2 p.Ala45Val Uncertain significance ★★ ⚠ same condition
RAX2 p.Arg179Gly Uncertain significance ★★ ⚠ same condition
RAX2 p.Arg28Gln Uncertain significance ★★ ⚠ same condition
RAX2 p.Arg31His Uncertain significance ★★ ⚠ same condition
RAX2 p.His149Arg Uncertain significance ★★ ⚠ same condition
RAX2 p.Leu39Pro 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/rax2-p-138pg-3 (accessed [today's date]).

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