PHOX2B p.Pro229fs
c.684dup · rs2552096835 · VCV2633086
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP -0.015, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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
- PHOX2B
- Protein
- p.Pro229fs
- Coding
- c.684dup
- MANE Select
- NM_003924
- dbSNP
- rs2552096835
- Type
- Duplication
- Location
- chr4:41746067 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.94 · 5 PDB
- Residue 229
- the 'disordered' region
Disease context
Similar variants
- PHOX2B p.Ala256_Ala260dup Pathogenic ★★ same condition
- PHOX2B p.Ser207fs Pathogenic ★★ same condition
- PHOX2B p.Pro229Thr Uncertain significance ★★ ⚠ same residue
- PHOX2B p.Pro229= Likely benign ★★ same residue
- PHOX2B p.Pro229His Uncertain significance ★ ⚠ same residue
- PHOX2B p.Pro229Ser Uncertain significance ★ ⚠ same residue
- PHOX2B p.Gly270fs Likely pathogenic same condition
- PHOX2B p.Arg128Trp 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/phox2b-p-pro229fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown