Is POMC p.Phe82Val (c.244T>G) pathogenic?

POMC p.Phe82Val (c.244T>G) is classified Uncertain significance in POMC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-24). AlphaMissense: likely pathogenic (0.8038); Ultra-rare (popmax 0.0195%, eas); Associated with POMC-related disorder.

What condition is associated with POMC p.Phe82Val (c.244T>G)?

POMC p.Phe82Val (c.244T>G) is associated with POMC-related disorder (ClinVar).

How common is POMC p.Phe82Val (c.244T>G) in the general population?

POMC p.Phe82Val (c.244T>G) is ultra-rare (popmax 0.0195%, eas) (gnomAD).

What do computational predictors say about POMC p.Phe82Val (c.244T>G)?

AlphaMissense predicts likely pathogenic (score 0.8038) — an in-silico prediction, not a clinical call.

POMC p.Phe82Val

c.244T>G · rs755926365 · VCV2635945

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

POMC-related disorder

Computational evidence

Protein change
AlphaMissense	0.8038	likely pathogenic
REVEL	0.757	pathogenic-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 3,688 bp · p 0.00022 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0195% East Asian · 8/41,070 alleles

Filtering AF 0.00964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00702%

Overall 0.000901% 14/1,553,750 alleles · ultra-rare exomes 13/1,402,008 · genomes 1/151,742 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0195%	5,134
Admixed American	0.00389%	25,702
Remaining individualsnot grpmax-eligible	0.00332%	30,090
African / African-American	0.00137%	72,734
European (non-Finnish)	8.7e-05%	1,149,466

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.Phe82Val
Coding: c.244T>G
MANE Select: NM_000939
dbSNP: rs755926365
Type: single nucleotide variant
Location: chr2:25161641 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.47 · 13 PDB
Residue 82: 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-phe82val (accessed [today's date]).

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