PHOX2B p.Arg115=
c.345G>A · rs747055965 · VCV699647
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP -0.41, phastCons 1 |
| Overall | ||
| CADD | 10.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,076 alleles
Filtering AF
0.00107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000496%
Overall
0.000993%
16/1,610,588 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,076 |
| African / African-American | 0.00403% | 24,845 |
| South Asian | 0.0011% | 91,014 |
| European (non-Finnish) | 0.000932% | 107,239 |
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
- PHOX2B
- Protein
- p.Arg115=
- Coding
- c.345G>A
- MANE Select
- NM_003924
- dbSNP
- rs747055965
- Type
- single nucleotide variant
- Location
- chr4:41747433 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.94 · 5 PDB
- Residue 115
- a DNA-binding region; an α-helix
Similar variants
- PHOX2B p.Arg115Lys Uncertain significance ★★ same residue
- PHOX2B p.Arg115Thr Uncertain significance ★★ ⚠ same residue
- PHOX2B p.Arg115Met Uncertain significance ★ ⚠ same residue
- PHOX2B c.241+1G>A Likely pathogenic ★★ same condition
- 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-arg115 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown