PHOX2B p.Lys238=
c.714G>A · rs1553897810 · VCV535781
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 9.89e-05%, nfe)
Conditions
1
Haddad syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.058 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.57 | GERP -0.31, phastCons 0.1 |
| Overall | ||
| CADD | 6.779 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.89e-05%
European (non-Finnish) · 1/1,011,036 alleles
Overall
8.93e-05%
1/1,119,460 alleles · very rare
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.Lys238=
- Coding
- c.714G>A
- MANE Select
- NM_003924
- dbSNP
- rs1553897810
- Type
- single nucleotide variant
- Location
- chr4:41746038 (GRCh38)
- Gene constraint
- LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 61.94 · 5 PDB
- Residue 238
- the 'disordered' region
Similar variants
- PHOX2B p.Lys238Asn Uncertain significance ★★ ⚠ same residue
- PHOX2B p.Lys238Arg Uncertain significance ★ ⚠ same residue
- PHOX2B p.Lys238Ter Likely pathogenic ★ same residue
- PHOX2B p.Lys238Gln 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.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-lys238 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown