Is COMP p.Asp357Phe (c.1069_1070delinsTT) pathogenic?

COMP p.Asp357Phe (c.10691070delinsTT) is classified Likely pathogenic in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Absent from gnomAD.

How common is COMP p.Asp357Phe (c.1069_1070delinsTT) in the general population?

COMP p.Asp357Phe (c.1069_1070delinsTT) is absent from gnomAD (gnomAD).

COMP p.Asp357Phe

c.1069_1070delinsTT · rs2512850157 · VCV2696896

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic

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.Asp357Phe
Coding: c.1069_1070delinsTT
MANE Select: NM_000095
dbSNP: rs2512850157
Type: Indel
Location: chr19:18787556 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 357: the 'disordered' region; a disulfide bond; a UniProt-annotated variant site (in psach)

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

Similar variants

COMP p.Asn291delinsCysAlaArgPro Likely pathogenic ★ same type
COMP p.Asn409_Gln412delinsLysCysProPro Uncertain significance ★ same type
COMP p.Asp319Tyr Uncertain significance ★ same type
COMP p.Asp401_Ile403delinsLeu 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-asp357phe (accessed [today's date]).

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