Is TIMP3 p.Ser130= (c.390C>T) pathogenic?

TIMP3 p.Ser130= (c.390C>T) is classified Likely benign in TIMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). Very rare (popmax 0.00167%, amr).

How common is TIMP3 p.Ser130= (c.390C>T) in the general population?

TIMP3 p.Ser130= (c.390C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

TIMP3 p.Ser130=

c.390C>T · rs1226724143 · VCV1534427

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

⚠ 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 0.3	GERP 0.44, phastCons 0.98
Overall
CADD	10.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Overall 0.000124% 2/1,614,060 alleles · very rare exomes 1/1,461,890 · genomes 1/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
Finnishnot grpmax-eligible	0.00156%	64,038

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.Ser130=
Coding: c.390C>T
MANE Select: NM_000362
dbSNP: rs1226724143
Type: single nucleotide variant
Location: chr22:32858090 (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-ser130 (accessed [today's date]).

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