Is PHOX2A p.Ser19= (c.57C>T) pathogenic?

PHOX2A p.Ser19= (c.57C>T) is classified Likely benign in PHOX2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-20). Very rare (popmax 0.000586%, nfe).

How common is PHOX2A p.Ser19= (c.57C>T) in the general population?

PHOX2A p.Ser19= (c.57C>T) is very rare (popmax 0.000586%, nfe) (gnomAD).

PHOX2A p.Ser19=

c.57C>T · VCV4912985

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000586%, nfe)

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 3.8	GERP -3.5, phastCons 1
Overall
CADD	13.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000586% European (non-Finnish) · 6/1,024,262 alleles

Filtering AF 0.000211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000457% 6/1,312,406 alleles · very rare exomes 4/1,160,304 · genomes 2/152,102 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PHOX2A
Protein: p.Ser19=
Coding: c.57C>T
MANE Select: NM_005169
Type: single nucleotide variant
Location: chr11:72243948 (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

Similar variants

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
PHOX2A p.Ala61Asp 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-ser19 (accessed [today's date]).

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