Is POMP c.101+9G>A pathogenic?

POMP c.101+9G>A is classified Benign/Likely benign in POMP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). Rare (popmax 0.465%, mid); Associated with proteasome-associated autoinflammatory syndrome 2.

What condition is associated with POMP c.101+9G>A?

POMP c.101+9G>A is associated with proteasome-associated autoinflammatory syndrome 2, keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (ClinVar).

How common is POMP c.101+9G>A in the general population?

POMP c.101+9G>A is rare (popmax 0.465%, mid) (gnomAD).

POMP c.101+9G>A

Q: How is Proteasome-associated autoinflammatory syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs116855705 · VCV1168426

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.465%, mid)

Conditions

proteasome-associated autoinflammatory syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.61	GERP -3.2
Non-coding constraint	Z 1.01	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.465% Middle Eastern · 28/6,016 alleles

Filtering AF 0.406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.389%

Overall 0.284% 4,513/1,590,590 alleles · rare exomes 4,122/1,438,314 · genomes 391/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.465%	215
Admixed American	0.45%	222
European (non-Finnish)	0.325%	307
Remaining individualsnot grpmax-eligible	0.295%	339
Finnishnot grpmax-eligible	0.173%	576
African / African-American	0.0927%	1,079
South Asian	0.0773%	1,294
Ashkenazi Jewishnot grpmax-eligible	0.0441%	2,267

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: POMP
Coding: c.101+9G>A
MANE Select: NM_015932
dbSNP: rs116855705
Type: single nucleotide variant
Location: chr13:28662516 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB

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

Disease context

proteasome-associated autoinflammatory syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome

For Proteasome-associated autoinflammatory syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

POMP p.Leu31Phe Uncertain significance ★★ ⚠ same condition
POMP c.265-1G>C Conflicting classifications of pathogenicity ★ same condition
POMP p.Ile112fs Pathogenic ★★ same condition
POMP p.Glu115fs Pathogenic same condition
POMP p.Phe114fs Pathogenic same condition
POMP p.Arg32Gln Uncertain significance ★★ ⚠ same type
POMP p.Arg32Trp Uncertain significance ★★ ⚠ same type
POMP p.Asn108His Uncertain significance ★★ ⚠ same type

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/pomp-c-101-plus-9g-a (accessed [today's date]).

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