Is RAX2 p.Ala94= (c.282C>T) pathogenic?

RAX2 p.Ala94= (c.282C>T) is classified Benign/Likely benign in RAX2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). Rare (popmax 0.739%, eas); Associated with cone-rod dystrophy 11.

What condition is associated with RAX2 p.Ala94= (c.282C>T)?

RAX2 p.Ala94= (c.282C>T) is associated with cone-rod dystrophy 11, age related macular degeneration 6 (ClinVar).

How common is RAX2 p.Ala94= (c.282C>T) in the general population?

RAX2 p.Ala94= (c.282C>T) is rare (popmax 0.739%, eas) (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.Ala94=

c.282C>T · rs201021639 · VCV328966

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.739%, eas)

Conditions

cone-rod dystrophy 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.03	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -3.6
Overall
CADD	0.624	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.739% East Asian · 308/41,704 alleles

Filtering AF 0.671% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.644%

Overall 0.0302% 466/1,543,222 alleles · rare exomes 386/1,390,956 · genomes 80/152,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.739%	135
Remaining individualsnot grpmax-eligible	0.0398%	2,513
Middle Eastern	0.0178%	5,618
South Asian	0.0141%	7,072
European (non-Finnish)	0.0101%	9,926
Admixed American	0.00388%	25,758
African / African-American	0.00272%	36,783
Finnishnot grpmax-eligible	0.00224%	44,558

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.Ala94=
Coding: c.282C>T
MANE Select: NM_001319074
dbSNP: rs201021639
Type: single nucleotide variant
Location: chr19:3770894 (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

Also linked: age related macular degeneration 6

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 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.Arg87Gln 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-ala94 (accessed [today's date]).

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