Is PHOX2B p.Ala79Val (c.236C>T) pathogenic?

PHOX2B p.Ala79Val (c.236C>T) is classified Uncertain significance in PHOX2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-24). AlphaMissense: likely benign (0.2651); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PHOX2B p.Ala79Val (c.236C>T)?

PHOX2B p.Ala79Val (c.236C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PHOX2B p.Ala79Val (c.236C>T) in the general population?

PHOX2B p.Ala79Val (c.236C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHOX2B p.Ala79Val (c.236C>T)?

AlphaMissense predicts likely benign (score 0.2651) — an in-silico prediction, not a clinical call.

PHOX2B p.Ala79Val

c.236C>T · rs2552097157 · VCV2625342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2651 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

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
AlphaMissense	0.2651	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,190 bp · p 2e-05 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala79Val
Coding: c.236C>T
MANE Select: NM_003924
dbSNP: rs2552097157
Type: single nucleotide variant
Location: chr4:41748375 (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

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-ala79val (accessed [today's date]).

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