Is PRRX1 p.Arg92fs (c.266_269dup) pathogenic?

PRRX1 p.Arg92fs (c.266269dup) is classified Pathogenic in PRRX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-04-01). No gnomAD frequency available for this variant; Associated with agnathia-otocephaly complex.

What condition is associated with PRRX1 p.Arg92fs (c.266_269dup)?

PRRX1 p.Arg92fs (c.266_269dup) is associated with agnathia-otocephaly complex (ClinVar).

How common is PRRX1 p.Arg92fs (c.266_269dup) in the general population?

PRRX1 p.Arg92fs (c.266_269dup) is no gnomAD frequency available for this variant (gnomAD).

PRRX1 p.Arg92fs

c.266_269dup · rs398122375 · VCV50497

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

agnathia-otocephaly complex

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRRX1
Protein: p.Arg92fs
Coding: c.266_269dup
MANE Select: NM_022716
dbSNP: rs398122375
Type: Duplication
Location: chr1:170719746 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 66.38
Residue 92: the 'disordered' region

Full PRRX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

agnathia-otocephaly complex — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRRX1 p.Ala184Val Uncertain significance ★ ⚠ same condition
PRRX1 p.Arg115Trp Uncertain significance ★ ⚠ same condition
PRRX1 p.Arg129Ser Uncertain significance ★ ⚠ same condition
PRRX1 p.Phe113Leu Uncertain significance ★ ⚠ same condition
PRRX1 p.Val175Met Uncertain significance ★ ⚠ same condition
PRRX1 p.Ala231Pro Pathogenic same condition
PRRX1 p.Leu106Pro Likely pathogenic same condition
PRRX1 p.Lys90fs Pathogenic 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/prrx1-p-arg92fs (accessed [today's date]).

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