Is RAX2 p.Arg44Gln (c.131G>A) pathogenic?

RAX2 p.Arg44Gln (c.131G>A) is classified Conflicting classifications of pathogenicity in RAX2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-14). AlphaMissense: likely benign (0.094); Ultra-rare (popmax 0.01%, amr); Associated with cone-rod dystrophy 11.

What condition is associated with RAX2 p.Arg44Gln (c.131G>A)?

RAX2 p.Arg44Gln (c.131G>A) is associated with cone-rod dystrophy 11, age related macular degeneration 6 (ClinVar).

How common is RAX2 p.Arg44Gln (c.131G>A) in the general population?

RAX2 p.Arg44Gln (c.131G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

How is Cone rod dystrophy inherited?

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

What do computational predictors say about RAX2 p.Arg44Gln (c.131G>A)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

RAX2 p.Arg44Gln

c.131G>A · rs370757303 · VCV892560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

cone-rod dystrophy 11

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.504	indeterminate
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.045	GERP 0.95, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 1,118 bp · p 0.83 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,894 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00267% 43/1,612,808 alleles · ultra-rare exomes 36/1,460,616 · genomes 7/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,982
Remaining individualsnot grpmax-eligible	0.0032%	31,222
European (non-Finnish)	0.00271%	36,868
African / African-American	0.00267%	37,462
East Asian	0.00223%	44,852

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.Arg44Gln
Coding: c.131G>A
MANE Select: NM_001319074
dbSNP: rs370757303
Type: single nucleotide variant
Location: chr19:3771612 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 71.72
Residue 44: a DNA-binding region

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 p.Arg44Trp Uncertain significance ★★ ⚠ same residue
RAX2 p.Arg44Gly Uncertain significance ★ ⚠ same residue
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

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-arg44gln (accessed [today's date]).

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