Is RAX p.Thr50Pro (c.148A>C) pathogenic?

RAX p.Thr50Pro (c.148A>C) is classified Benign/Likely benign in RAX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-27). AlphaMissense: likely benign (0.0632); Low-frequency (popmax 3.5%, afr); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Thr50Pro (c.148A>C)?

RAX p.Thr50Pro (c.148A>C) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Thr50Pro (c.148A>C) in the general population?

RAX p.Thr50Pro (c.148A>C) is low-frequency (popmax 3.5%, afr) (gnomAD).

What do computational predictors say about RAX p.Thr50Pro (c.148A>C)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

RAX p.Thr50Pro

c.148A>C · rs150622912 · VCV707012

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.5%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

isolated microphthalmia 3

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.39	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 0.28	GERP -3.6, phastCons 0.22
Regional constraint	o/e 1.05	unconstrained · MANE · 4,199 bp · p 0.25 · regional, not allelic
Overall
CADD	3.134	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 3.5% African / African-American · 2,554/73,072 alleles

Filtering AF 3.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.34%

Overall 0.2% 3,064/1,534,878 alleles · low-frequency exomes 1,550/1,382,604 · genomes 1,514/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.5%	29
Middle Eastern	0.387%	259
Remaining individualsnot grpmax-eligible	0.315%	317
Admixed American	0.229%	436
South Asian	0.0167%	6,002
European (non-Finnish)	0.0144%	6,948
Ashkenazi Jewishnot grpmax-eligible	0.0035%	28,612
East Asian	0.00245%	40,844

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.Thr50Pro
Coding: c.148A>C
MANE Select: NM_013435
dbSNP: rs150622912
Type: single nucleotide variant
Location: chr18:59273059 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 50: the 'disordered' region

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

Disease context

isolated microphthalmia 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-thr50pro (accessed [today's date]).

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