Is RAX2 p.Ala144= (c.432G>A) pathogenic?

RAX2 p.Ala144= (c.432G>A) is classified Conflicting classifications of pathogenicity in RAX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.257%, mid); Associated with age related macular degeneration 6.

What condition is associated with RAX2 p.Ala144= (c.432G>A)?

RAX2 p.Ala144= (c.432G>A) is associated with age related macular degeneration 6, cone-rod dystrophy 11 (ClinVar).

How common is RAX2 p.Ala144= (c.432G>A) in the general population?

RAX2 p.Ala144= (c.432G>A) is rare (popmax 0.257%, mid) (gnomAD).

RAX2 p.Ala144=

c.432G>A · rs149918940 · VCV262101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.257%, mid)

Conditions

age related macular degeneration 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -2.5
Overall
CADD	3.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.257% Middle Eastern · 14/5,454 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.177%

Overall 0.152% 2,332/1,532,820 alleles · rare exomes 2,165/1,380,518 · genomes 167/152,302 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.257%	390
European (non-Finnish)	0.186%	538
Admixed American	0.132%	759
Remaining individualsnot grpmax-eligible	0.11%	906
Finnishnot grpmax-eligible	0.0356%	2,809
South Asian	0.0262%	3,814
African / African-American	0.0248%	4,032
East Asian	0.00247%	40,554

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.Ala144=
Coding: c.432G>A
MANE Select: NM_001319074
dbSNP: rs149918940
Type: single nucleotide variant
Location: chr19:3770744 (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

Also linked: cone-rod dystrophy 11

Similar variants

RAX2 p.Ala144Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
RAX2 p.Ala144Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala144 (accessed [today's date]).

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