Is PHOX2B p.Thr23= (c.69C>G) pathogenic?

PHOX2B p.Thr23= (c.69C>G) is classified Likely benign in PHOX2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-30). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PHOX2B p.Thr23= (c.69C>G)?

PHOX2B p.Thr23= (c.69C>G) is associated with hereditary neoplastic syndrome, Haddad syndrome (ClinVar).

How common is PHOX2B p.Thr23= (c.69C>G) in the general population?

PHOX2B p.Thr23= (c.69C>G) is absent from gnomAD v4.1 (gnomAD).

PHOX2B p.Thr23=

c.69C>G · rs1303902128 · VCV1141055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic 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 3.8	GERP -1.5, phastCons 1
Overall
CADD	14.92	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.Thr23=
Coding: c.69C>G
MANE Select: NM_003924
dbSNP: rs1303902128
Type: single nucleotide variant
Location: chr4:41748542 (GRCh38)

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

Also linked: Haddad 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-thr23 (accessed [today's date]).

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