Is COMP p.Gly307Val (c.920G>T) pathogenic?

COMP p.Gly307Val (c.920G>T) is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: ambiguous (0.4735); Very rare (popmax 6.85e-05%).

How common is COMP p.Gly307Val (c.920G>T) in the general population?

COMP p.Gly307Val (c.920G>T) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about COMP p.Gly307Val (c.920G>T)?

AlphaMissense predicts ambiguous (score 0.4735) — an in-silico prediction, not a clinical call.

COMP p.Gly307Val

c.920G>T · VCV4742274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4735	ambiguous
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -13.95	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,890 alleles · very rare

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.Gly307Val
Coding: c.920G>T
MANE Select: NM_000095
Type: single nucleotide variant
Location: chr19:18788267 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 307: a β-strand; the 'disordered' region; a disulfide bond

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

Similar variants

COMP p.Gly307Ala Uncertain significance ★★ ⚠ same residue
COMP p.Gly307Asp Uncertain significance ★ ⚠ same residue
COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asn555Lys Pathogenic/Likely pathogenic ★★ same type
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same type
COMP p.Asp273Val 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-gly307val (accessed [today's date]).

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