Is COMP p.Met1Val (c.1A>G) pathogenic?

COMP p.Met1Val (c.1A>G) is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-17). Very rare (popmax 8.54e-05%, nfe); Associated with carpal tunnel syndrome 2.

What condition is associated with COMP p.Met1Val (c.1A>G)?

COMP p.Met1Val (c.1A>G) is associated with carpal tunnel syndrome 2 (ClinVar).

How common is COMP p.Met1Val (c.1A>G) in the general population?

COMP p.Met1Val (c.1A>G) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

COMP p.Met1Val

c.1A>G · rs2145906023 · VCV1184999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Conditions

carpal tunnel syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.577	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.4, phastCons 1
Overall
CADD	18.79	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,171,562 alleles

Overall 6.28e-05% 1/1,592,218 alleles · very rare exomes 1/1,440,030 · genomes 0/152,188 · joint denominator

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.Met1Val
Coding: c.1A>G
MANE Select: NM_000095
dbSNP: rs2145906023
Type: single nucleotide variant
Location: chr19:18791269 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB

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

Disease context

carpal tunnel syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp385Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp399Asn Likely pathogenic ★★ same condition
COMP p.Ala171Thr Benign/Likely benign ★★ same condition
COMP p.Thr585= Benign ★★ same condition
COMP p.Thr585Arg Pathogenic ★ same condition
COMP p.Asp509Ala Uncertain significance ★ ⚠ same condition
COMP p.Gln616His Uncertain significance ★ ⚠ 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-met1val (accessed [today's date]).

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