Is RAX p.Ala267Val (c.800C>T) pathogenic?

RAX p.Ala267Val (c.800C>T) is classified Uncertain significance in RAX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0771); Rare (popmax 0.233%, mid); Associated with Inborn genetic diseases.

What condition is associated with RAX p.Ala267Val (c.800C>T)?

RAX p.Ala267Val (c.800C>T) is associated with Inborn genetic diseases, isolated microphthalmia 3 (ClinVar).

How common is RAX p.Ala267Val (c.800C>T) in the general population?

RAX p.Ala267Val (c.800C>T) is rare (popmax 0.233%, mid) (gnomAD).

What do computational predictors say about RAX p.Ala267Val (c.800C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

RAX p.Ala267Val

c.800C>T · rs760516983 · VCV959738

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.9, phastCons 0.82
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% Middle Eastern · 10/4,298 alleles

Filtering AF 0.126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0961%

Overall 0.0158% 238/1,505,938 alleles · rare exomes 210/1,354,434 · genomes 28/151,504 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.233%	430
African / African-American	0.0564%	1,773
Remaining individualsnot grpmax-eligible	0.0359%	2,784
Admixed American	0.0145%	6,914
South Asian	0.0136%	7,345
European (non-Finnish)	0.0131%	7,615
Finnishnot grpmax-eligible	0.00226%	44,208

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.Ala267Val
Coding: c.800C>T
MANE Select: NM_013435
dbSNP: rs760516983
Type: single nucleotide variant
Location: chr18:59269245 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 267: 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.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
RAX p.Gly56Ser 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-ala267val (accessed [today's date]).

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