Is COMP p.Glu493del (c.1476GGA[1]) pathogenic?

COMP p.Glu493del (c.1476GGA[1]) is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Very rare (popmax 8.48e-05%, nfe).

How common is COMP p.Glu493del (c.1476GGA[1]) in the general population?

COMP p.Glu493del (c.1476GGA[1]) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

COMP p.Glu493del

c.1476GGA[1] · rs770721341 · VCV2994403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.23	GERP -4
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,948 alleles

Overall 0.000373% 6/1,608,894 alleles · very rare exomes 5/1,457,832 · genomes 1/151,062 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,847
Remaining individualsnot grpmax-eligible	0.00321%	31,152
European (non-Finnish)grpmax	8.48e-05%	1,178,948

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: COMP
Protein: p.Glu493del
Coding: c.1476GGA[1]
MANE Select: NM_000095
dbSNP: rs770721341
Type: Microsatellite
Location: chr19:18785973 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 493: the 'disordered' region

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

Similar variants

COMP p.Asp374del Pathogenic/Likely pathogenic ★★ same type
COMP p.Asp473del Pathogenic ★★ same type
COMP p.Asp473dup Pathogenic/Likely pathogenic ★★ same type
COMP p.Glu457del Pathogenic/Likely pathogenic ★★ same type
COMP p.Gly320_Val321insAspGly Likely pathogenic ★ same type
COMP p.Asp374_Ile375insAsp Uncertain significance ★ same type
COMP p.Asp471_Asp473del Uncertain significance ★ same type
COMP p.Cys266fs 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/comp-p-glu493del (accessed [today's date]).

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