Is POMC p.Ser9= (c.27G>A) pathogenic?

POMC p.Ser9= (c.27G>A) is classified Likely benign in POMC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 0.0022%, sas); Associated with POMC-related disorder.

What condition is associated with POMC p.Ser9= (c.27G>A)?

POMC p.Ser9= (c.27G>A) is associated with POMC-related disorder (ClinVar).

How common is POMC p.Ser9= (c.27G>A) in the general population?

POMC p.Ser9= (c.27G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

POMC p.Ser9=

c.27G>A · VCV3353018

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

POMC-related disorder

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 -7.1	GERP -3.6
Overall
CADD	4.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,614,070 alleles · very rare exomes 18/1,461,724 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00127%	78,669

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: POMC
Protein: p.Ser9=
Coding: c.27G>A
MANE Select: NM_000939
Type: single nucleotide variant
Location: chr2:25164746 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.47 · 13 PDB
Residue 9: a UniProt-annotated variant site (in)

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

Disease context

POMC-related disorder

Similar variants

POMC p.Ser9Leu Uncertain significance ★ ⚠ same residue
POMC p.Asn42Ser Uncertain significance ★ ⚠ same condition
POMC p.Asn91Ser Uncertain significance ★ ⚠ same condition
POMC p.Cys34Arg Uncertain significance ★ ⚠ same condition
POMC p.Ser95Asn Uncertain significance ★ ⚠ same condition
POMC p.Thr39= Conflicting classifications of pathogenicity ★ same condition
POMC c.132+5G>A Uncertain significance same condition
POMC p.Ala212Val 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/pomc-p-ser9 (accessed [today's date]).

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