PHOX2B p.Ala241=
c.723A>C · rs1204677453 · VCV1757841
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hereditary neoplastic syndrome
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 -2 | GERP -3 |
| Overall | ||
| CADD | 3.669 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PHOX2B
- Protein
- p.Ala241=
- Coding
- c.723A>C
- MANE Select
- NM_003924
- dbSNP
- rs1204677453
- Type
- single nucleotide variant
- Location
- chr4:41746029 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.94 · 5 PDB
- Residue 241
- a UniProt-annotated variant site (in cchs1); the 'disordered' region; an α-helix
Similar variants
- PHOX2B p.Ala241Glu Uncertain significance ★ ⚠ same residue
- PHOX2B p.Ala241Ser Uncertain significance ★ ⚠ same residue
- PHOX2B p.Ala241Pro Uncertain significance ★ ⚠ same residue
- PHOX2B p.Ala241Thr Uncertain significance ★ ⚠ same residue
- PHOX2B c.242-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PHOX2B p.Arg141Gln Pathogenic/Likely pathogenic ★★ same condition
- PHOX2B p.Gln98Ter Pathogenic ★★ same condition
- PHOX2B p.Tyr83Ter Pathogenic/Likely 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/phox2b-p-ala241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown