Is PHOX2B p.Ala151= (c.453C>A) pathogenic?

PHOX2B p.Ala151= (c.453C>A) is classified Likely benign in PHOX2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-10). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PHOX2B p.Ala151= (c.453C>A)?

PHOX2B p.Ala151= (c.453C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PHOX2B p.Ala151= (c.453C>A) in the general population?

PHOX2B p.Ala151= (c.453C>A) is absent from gnomAD v4.1 (gnomAD).

PHOX2B p.Ala151=

c.453C>A · rs1577559389 · VCV1741319

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.
REVEL	0.082	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.84, phastCons 1
Overall
CADD	14.21	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.Ala151=
Coding: c.453C>A
MANE Select: NM_003924
dbSNP: rs1577559389
Type: single nucleotide variant
Location: chr4:41746299 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.94 · 5 PDB
Residue 151: 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.Ala151Val Uncertain significance ★★ ⚠ same residue
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

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-ala151 (accessed [today's date]).

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