Is POMC p.Ser243= (c.729C>T) pathogenic?

POMC p.Ser243= (c.729C>T) is classified Likely benign in POMC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-14). Very rare (popmax 0.005%, amr); Associated with POMC-related disorder.

What condition is associated with POMC p.Ser243= (c.729C>T)?

POMC p.Ser243= (c.729C>T) is associated with POMC-related disorder (ClinVar).

How common is POMC p.Ser243= (c.729C>T) in the general population?

POMC p.Ser243= (c.729C>T) is very rare (popmax 0.005%, amr) (gnomAD).

POMC p.Ser243=

c.729C>T · rs766097368 · VCV3055667

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -6.7	GERP -2.9
Overall
CADD	2.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00291% 47/1,613,792 alleles · very rare exomes 45/1,461,600 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
European (non-Finnish)	0.00364%	27,442
East Asian	0.00223%	44,878

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.Ser243=
Coding: c.729C>T
MANE Select: NM_000939
dbSNP: rs766097368
Type: single nucleotide variant
Location: chr2:25161156 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.47 · 13 PDB
Residue 243: a β-strand

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

Disease context

POMC-related disorder

Similar variants

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
POMC p.Arg186Trp 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-ser243 (accessed [today's date]).

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