Is RAX p.Lys172= (c.516G>A) pathogenic?

RAX p.Lys172= (c.516G>A) is classified Likely benign in RAX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Ultra-rare (popmax 0.0571%, nfe); Associated with isolated microphthalmia 3.

What condition is associated with RAX p.Lys172= (c.516G>A)?

RAX p.Lys172= (c.516G>A) is associated with isolated microphthalmia 3 (ClinVar).

How common is RAX p.Lys172= (c.516G>A) in the general population?

RAX p.Lys172= (c.516G>A) is ultra-rare (popmax 0.0571%, nfe) (gnomAD).

RAX p.Lys172=

c.516G>A · rs144080426 · VCV707168

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0571%, nfe)

Conditions

isolated microphthalmia 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.81, phastCons 0.94
Overall
CADD	12.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0571% European (non-Finnish) · 674/1,180,058 alleles

Filtering AF 0.0535% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.052%

Overall 0.0433% 699/1,614,142 alleles · ultra-rare exomes 666/1,461,886 · genomes 33/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0571%	1,751
Remaining individualsnot grpmax-eligible	0.0176%	5,681
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.0125%	8,005
Admixed American	0.00333%	30,007
African / African-American	0.00267%	37,479
South Asian	0.0011%	91,090

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.Lys172=
Coding: c.516G>A
MANE Select: NM_013435
dbSNP: rs144080426
Type: single nucleotide variant
Location: chr18:59272388 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.10
Residue 172: a DNA-binding 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-lys172 (accessed [today's date]).

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