Is RAX p.Pro279Ala (c.835C>G) pathogenic?

RAX p.Pro279Ala (c.835C>G) is classified Uncertain significance in RAX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.0612); Very rare (popmax 0.00499%, eas); Associated with Inborn genetic diseases.

What condition is associated with RAX p.Pro279Ala (c.835C>G)?

RAX p.Pro279Ala (c.835C>G) is associated with Inborn genetic diseases, isolated microphthalmia 3 (ClinVar).

How common is RAX p.Pro279Ala (c.835C>G) in the general population?

RAX p.Pro279Ala (c.835C>G) is very rare (popmax 0.00499%, eas) (gnomAD).

What do computational predictors say about RAX p.Pro279Ala (c.835C>G)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

RAX p.Pro279Ala

c.835C>G · rs886054025 · VCV327531

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00499%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.5	GERP 0.91, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	18.77	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 0.00499% East Asian · 2/40,056 alleles

Filtering AF 0.000827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00031%

Overall 0.000196% 3/1,530,578 alleles · very rare exomes 2/1,378,610 · genomes 1/151,968 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00499%	20,028
Remaining individualsnot grpmax-eligible	0.00168%	59,492

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.Pro279Ala
Coding: c.835C>G
MANE Select: NM_013435
dbSNP: rs886054025
Type: single nucleotide variant
Location: chr18:59269210 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 279: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: isolated microphthalmia 3

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-pro279ala (accessed [today's date]).

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