Is POMC p.Arg104= (c.312C>T) pathogenic?

POMC p.Arg104= (c.312C>T) is classified Likely benign in POMC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-19). Ultra-rare (popmax 0.0167%, eas); Associated with POMC-related disorder.

What condition is associated with POMC p.Arg104= (c.312C>T)?

POMC p.Arg104= (c.312C>T) is associated with POMC-related disorder (ClinVar).

How common is POMC p.Arg104= (c.312C>T) in the general population?

POMC p.Arg104= (c.312C>T) is ultra-rare (popmax 0.0167%, eas) (gnomAD).

POMC p.Arg104=

c.312C>T · rs1020449183 · VCV3058717

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, eas)

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 -0.18	GERP -2.3, phastCons 0.091
Overall
CADD	9.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% East Asian · 7/42,026 alleles

Filtering AF 0.00779% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00553%

Overall 0.000901% 14/1,553,528 alleles · ultra-rare exomes 10/1,402,640 · genomes 4/150,888 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0167%	6,004
Remaining individualsnot grpmax-eligible	0.00333%	29,987
African / African-American	0.00281%	35,525
European (non-Finnish)	0.000261%	383,322

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.Arg104=
Coding: c.312C>T
MANE Select: NM_000939
dbSNP: rs1020449183
Type: single nucleotide variant
Location: chr2:25161573 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.47 · 13 PDB
Residue 104: the 'disordered' region

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

Disease context

POMC-related disorder

Similar variants

POMC p.Arg104Ser 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-arg104 (accessed [today's date]).

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