Is POMP p.Phe114fs (c.342_348delinsACC) pathogenic?

POMP p.Phe114fs (c.342348delinsACC) is classified Pathogenic in POMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-07-17). No gnomAD frequency available for this variant; Associated with proteasome-associated autoinflammatory syndrome 2.

What condition is associated with POMP p.Phe114fs (c.342_348delinsACC)?

POMP p.Phe114fs (c.342_348delinsACC) is associated with proteasome-associated autoinflammatory syndrome 2 (ClinVar).

How common is POMP p.Phe114fs (c.342_348delinsACC) in the general population?

POMP p.Phe114fs (c.342_348delinsACC) is no gnomAD frequency available for this variant (gnomAD).

POMP p.Phe114fs

Q: How is Proteasome-associated autoinflammatory syndrome inherited?

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

c.342_348delinsACC · rs1555257076 · VCV548960

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

proteasome-associated autoinflammatory syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 16 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: POMP
Protein: p.Phe114fs
Coding: c.342_348delinsACC
MANE Select: NM_015932
dbSNP: rs1555257076
Type: Indel
Location: chr13:28672416 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 81.76 · 11 PDB
Residue 114: an α-helix

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

For Proteasome-associated autoinflammatory syndrome (Orphanet):

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

Similar variants

POMP p.Ile112fs Pathogenic ★★ same condition
POMP p.Leu31Phe Uncertain significance ★★ ⚠ same condition
POMP c.101+9G>A Benign/Likely benign ★★ same condition
POMP c.265-1G>C Conflicting classifications of pathogenicity ★ same condition
POMP p.Glu115fs Pathogenic 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/pomp-p-phe114fs (accessed [today's date]).

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