Is PHOX2A p.Ala68Thr (c.202G>A) pathogenic?

PHOX2A p.Ala68Thr (c.202G>A) is classified Uncertain significance in PHOX2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-23). AlphaMissense: likely benign (0.0823); No allele count reported in gnomAD v4.1 (AN 1,249,154); Associated with PHOX2A-related disorder.

What condition is associated with PHOX2A p.Ala68Thr (c.202G>A)?

PHOX2A p.Ala68Thr (c.202G>A) is associated with PHOX2A-related disorder (ClinVar).

How common is PHOX2A p.Ala68Thr (c.202G>A) in the general population?

PHOX2A p.Ala68Thr (c.202G>A) is no allele count reported in gnomAD v4.1 (AN 1,249,154) (gnomAD).

What do computational predictors say about PHOX2A p.Ala68Thr (c.202G>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

PHOX2A p.Ala68Thr

c.202G>A · VCV3349196

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,249,154)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PHOX2A-related disorder

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,947 bp · p 0.076 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,249,154). 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: PHOX2A
Protein: p.Ala68Thr
Coding: c.202G>A
MANE Select: NM_005169
Type: single nucleotide variant
Location: chr11:72243803 (GRCh38)
Gene constraint: LOEUF 1.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.49

Full PHOX2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHOX2A-related disorder

Similar variants

PHOX2A p.Ala68Pro Uncertain significance ★ ⚠ same residue
PHOX2A p.Ala72Val Uncertain significance ★★ ⚠ same type
PHOX2A c.-19G>A Benign ★★ same type
PHOX2A p.Leu52= Benign ★★ same type
PHOX2A p.Ala152Gly Uncertain significance ★ ⚠ same type
PHOX2A p.Ala158Glu Uncertain significance ★ ⚠ same type
PHOX2A p.Ala278Asp Uncertain significance ★ same type
PHOX2A p.Ala278Val Uncertain significance ★ ⚠ same type

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/phox2a-p-ala68thr (accessed [today's date]).

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