Is COMP p.Gly427fs (c.1279_1291del) pathogenic?

COMP p.Gly427fs (c.12791291del) is classified Likely pathogenic in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-18). Absent from gnomAD.

How common is COMP p.Gly427fs (c.1279_1291del) in the general population?

COMP p.Gly427fs (c.1279_1291del) is absent from gnomAD (gnomAD).

COMP p.Gly427fs

c.1279_1291del · rs878853098 · VCV235706

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	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: COMP
Protein: p.Gly427fs
Coding: c.1279_1291del
MANE Select: NM_000095
dbSNP: rs878853098
Type: Deletion
Location: chr19:18786255 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 427: the 'disordered' region; a disulfide bond; a UniProt-annotated variant site (in edm1)

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

Similar variants

COMP p.Gly427Ala Pathogenic/Likely pathogenic ★★ same residue
COMP p.Gly427Arg Likely pathogenic ★ same residue
COMP p.Gly427Glu Pathogenic ★ same residue
COMP p.Asp385del Likely pathogenic ★★ same type
COMP p.Glu341_Asp342del Pathogenic/Likely pathogenic ★★ same type
COMP c.1136-1_1144del Likely pathogenic ★ same type
COMP p.437DG[1] Likely pathogenic ★ same type
COMP p.Asn350_Asp372del Likely pathogenic ★ 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/comp-p-gly427fs (accessed [today's date]).

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