Is ADAMTS20 p.Gly826Val (c.2477G>T) pathogenic?

ADAMTS20 p.Gly826Val (c.2477G>T) is classified Uncertain significance in ADAMTS20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 8.48e-05%, nfe).

How common is ADAMTS20 p.Gly826Val (c.2477G>T) in the general population?

ADAMTS20 p.Gly826Val (c.2477G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ADAMTS20 p.Gly826Val

c.2477G>T · rs2498335895 · VCV3076874

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.
REVEL	0.576	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 198 kb · p 0.2 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,606 alleles

Overall 6.85e-05% 1/1,459,152 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: ADAMTS20
Protein: p.Gly826Val
Coding: c.2477G>T
MANE Select: NM_025003
dbSNP: rs2498335895
Type: single nucleotide variant
Location: chr12:43439738 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.35
Residue 826: the 'spacer' region

Full ADAMTS20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAMTS20 p.His183Leu Uncertain significance ★★ same type
ADAMTS20 p.Glu915Asp Benign ★★ same type
ADAMTS20 p.Gly985= Benign ★★ same type
ADAMTS20 p.Ala102Thr Uncertain significance ★ same type
ADAMTS20 p.Ala1479Thr Uncertain significance ★ same type
ADAMTS20 p.Ala1700Ser Uncertain significance ★ same type
ADAMTS20 p.Ala1797Ser Uncertain significance ★ same type
ADAMTS20 p.Ala431Thr 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/adamts20-p-gly826val (accessed [today's date]).

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