Is PHOX2B p.Phe51= (c.153T>C) pathogenic?

PHOX2B p.Phe51= (c.153T>C) is classified Likely benign in PHOX2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-26). No allele count reported in gnomAD v4.1 (AN 1,614,172); Associated with Haddad syndrome.

What condition is associated with PHOX2B p.Phe51= (c.153T>C)?

PHOX2B p.Phe51= (c.153T>C) is associated with Haddad syndrome, hereditary neoplastic syndrome (ClinVar).

How common is PHOX2B p.Phe51= (c.153T>C) in the general population?

PHOX2B p.Phe51= (c.153T>C) is no allele count reported in gnomAD v4.1 (AN 1,614,172) (gnomAD).

PHOX2B p.Phe51=

c.153T>C · rs1012348354 · VCV729370

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,172)

Conditions

Haddad syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.6	GERP 0.33, phastCons 1
Overall
CADD	16.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,172). 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.Phe51=
Coding: c.153T>C
MANE Select: NM_003924
dbSNP: rs1012348354
Type: single nucleotide variant
Location: chr4:41748458 (GRCh38)

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

Disease context

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

Also linked: hereditary neoplastic syndrome

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-phe51 (accessed [today's date]).

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