Is TIMP3 p.Arg43= (c.129G>A) pathogenic?

TIMP3 p.Arg43= (c.129G>A) is classified Likely benign in TIMP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-04). Ultra-rare (popmax 0.0281%, nfe).

How common is TIMP3 p.Arg43= (c.129G>A) in the general population?

TIMP3 p.Arg43= (c.129G>A) is ultra-rare (popmax 0.0281%, nfe) (gnomAD).

TIMP3 p.Arg43=

c.129G>A · rs374488332 · VCV1161664

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, 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 1.4	GERP 1.7, phastCons 1
Overall
CADD	9.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% European (non-Finnish) · 331/1,179,848 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0245%

Overall 0.0215% 347/1,613,528 alleles · ultra-rare exomes 330/1,461,356 · genomes 17/152,172 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0281%	3,564
Remaining individualsnot grpmax-eligible	0.0208%	4,803
Admixed American	0.00334%	29,982
African / African-American	0.00134%	74,904

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.Arg43=
Coding: c.129G>A
MANE Select: NM_000362
dbSNP: rs374488332
Type: single nucleotide variant
Location: chr22:32849459 (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-arg43 (accessed [today's date]).

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