Is PHOX2B p.Pro301= (c.903C>G) pathogenic?

PHOX2B p.Pro301= (c.903C>G) is classified Likely benign in PHOX2B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-22). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PHOX2B p.Pro301= (c.903C>G)?

PHOX2B p.Pro301= (c.903C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PHOX2B p.Pro301= (c.903C>G) in the general population?

PHOX2B p.Pro301= (c.903C>G) is absent from gnomAD v4.1 (gnomAD).

PHOX2B p.Pro301=

c.903C>G · rs2552096758 · VCV1765556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	13.91	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.Pro301=
Coding: c.903C>G
MANE Select: NM_003924
dbSNP: rs2552096758
Type: single nucleotide variant
Location: chr4:41745849 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.94 · 5 PDB

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 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
PHOX2B c.241+5G>A Uncertain significance ★★ same condition
PHOX2B c.429+4C>A Uncertain significance ★★ same condition
PHOX2B c.429+4C>T Uncertain significance ★★ same condition
PHOX2B p.Ala108Val Uncertain significance ★★ ⚠ 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-pro301 (accessed [today's date]).

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