Is PHOX2B p.Trp145Arg (c.432_433delinsTC) pathogenic?

PHOX2B p.Trp145Arg (c.432433delinsTC) is classified Uncertain significance in PHOX2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-03). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with PHOX2B p.Trp145Arg (c.432_433delinsTC)?

PHOX2B p.Trp145Arg (c.432_433delinsTC) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PHOX2B p.Trp145Arg (c.432_433delinsTC) in the general population?

PHOX2B p.Trp145Arg (c.432_433delinsTC) is no gnomAD frequency available for this variant (gnomAD).

PHOX2B p.Trp145Arg

c.432_433delinsTC · rs2552096908 · VCV1739695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.04	constrained · MANE · 1,081 bp · p 8.4e-07 · regional, not allelic

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: PHOX2B
Protein: p.Trp145Arg
Coding: c.432_433delinsTC
MANE Select: NM_003924
dbSNP: rs2552096908
Type: Indel
Location: chr4:41746319 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.94 · 5 PDB
Residue 145: a DNA-binding region; an α-helix

Full PHOX2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHOX2B p.Ala227Leu Uncertain significance ★★ same condition
PHOX2B p.Gly214Glu Uncertain significance ★★ same condition
PHOX2B p.Gln271Cys Uncertain significance ★ same condition
PHOX2B p.Ser293Lys Uncertain significance ★ same condition
PHOX2B c.242-1G>A Pathogenic/Likely pathogenic ★★ same condition
PHOX2B p.Ala256_Ala260dup Pathogenic ★★ same condition
PHOX2B p.Arg141Gln Pathogenic/Likely pathogenic ★★ same condition
PHOX2B p.Gln98Ter 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-trp145arg (accessed [today's date]).

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