Is COMP p.Gly122fs (c.361_364dup) pathogenic?

COMP p.Gly122fs (c.361364dup) is classified Likely pathogenic in COMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-25). Absent from gnomAD; Associated with COMP-related disorder.

What condition is associated with COMP p.Gly122fs (c.361_364dup)?

COMP p.Gly122fs (c.361_364dup) is associated with COMP-related disorder (ClinVar).

How common is COMP p.Gly122fs (c.361_364dup) in the general population?

COMP p.Gly122fs (c.361_364dup) is absent from gnomAD (gnomAD).

COMP p.Gly122fs

c.361_364dup · rs1601059597 · VCV800801

Likely pathogenic No assertion criteria

Classification

Likely 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

COMP-related disorder

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 4 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 1.8, 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.Gly122fs
Coding: c.361_364dup
MANE Select: NM_000095
dbSNP: rs1601059597
Type: Duplication
Location: chr19:18789967 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 122: the egf-like 1 domain; a disulfide bond

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

Disease context

COMP-related disorder

Similar variants

COMP p.Gly122= Uncertain significance ★ same residue
COMP p.Gly122Cys Uncertain significance ★ ⚠ same residue
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp385del Likely pathogenic ★★ same condition
COMP p.Asp401Asn Pathogenic ★★ same condition
COMP p.Asp458Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp473del 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/comp-p-gly122fs (accessed [today's date]).

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