Is TIMP3 p.Leu7= (c.21C>T) pathogenic?

TIMP3 p.Leu7= (c.21C>T) is classified Likely benign in TIMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-04). Very rare (popmax 0.000428%, nfe).

How common is TIMP3 p.Leu7= (c.21C>T) in the general population?

TIMP3 p.Leu7= (c.21C>T) is very rare (popmax 0.000428%, nfe) (gnomAD).

TIMP3 p.Leu7=

c.21C>T · rs2046600398 · VCV1633891

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000428%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.3	GERP -3.2
Overall
CADD	6.189	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000428% European (non-Finnish) · 5/1,166,892 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000317% 5/1,577,172 alleles · very rare exomes 5/1,424,932 · genomes 0/152,240 · 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: TIMP3
Protein: p.Leu7=
Coding: c.21C>T
MANE Select: NM_000362
dbSNP: rs2046600398
Type: single nucleotide variant
Location: chr22:32802022 (GRCh38)

Full TIMP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/timp3-p-leu7 (accessed [today's date]).

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