Is POMC p.Ser94= (c.282C>T) pathogenic?

POMC p.Ser94= (c.282C>T) is classified Benign/Likely benign in POMC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 29.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with obesity due to pro-opiomelanocortin deficiency.

What condition is associated with POMC p.Ser94= (c.282C>T)?

POMC p.Ser94= (c.282C>T) is associated with obesity due to pro-opiomelanocortin deficiency, obesity disorder (ClinVar).

POMC p.Ser94=

Q: How common is POMC p.Ser94= (c.282C>T) in the general population?

POMC p.Ser94= (c.282C>T) is common (popmax 29.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.282C>T · rs28930368 · VCV335356

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 29.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

obesity due to pro-opiomelanocortin deficiency

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 -0.015	GERP -2
Overall
CADD	4.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29.5% East Asian · 12,195/41,336 alleles

Filtering AF 29.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.9%

Overall 1.86% 28,993/1,556,648 alleles · common exomes 25,513/1,404,470 · genomes 3,480/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	29.5%	3
South Asian	9.17%	11
Finnishnot grpmax-eligible	4.38%	23
Admixed American	3.6%	28
Remaining individualsnot grpmax-eligible	2.73%	37
Middle Eastern	0.768%	130
Ashkenazi Jewishnot grpmax-eligible	0.736%	136
African / African-American	0.233%	429
European (non-Finnish)	0.216%	463

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.Ser94=
Coding: c.282C>T
MANE Select: NM_000939
dbSNP: rs28930368
Type: single nucleotide variant
Location: chr2:25161603 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.47 · 13 PDB
Residue 94: the 'disordered' region

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

Disease context

obesity due to pro-opiomelanocortin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: obesity disorder

Similar variants

POMC p.Ser94Gly Uncertain significance ★★ ⚠ same residue
POMC p.Ser94Arg Uncertain significance ⚠ same residue
POMC c.-11C>A Pathogenic ★★ same condition
POMC p.Ala164Val Uncertain significance ★★ ⚠ same condition
POMC p.Ala213Val Uncertain significance ★★ ⚠ same condition
POMC p.Arg145Cys Uncertain significance ★★ ⚠ same condition
POMC p.Arg145His Uncertain significance ★★ ⚠ same condition
POMC p.His143Gln 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-ser94 (accessed [today's date]).

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