Is TIMP3 p.Glu85= (c.255A>G) pathogenic?

TIMP3 p.Glu85= (c.255A>G) is classified Conflicting classifications of pathogenicity in TIMP3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-28). Very rare (popmax 0.00254%, nfe).

How common is TIMP3 p.Glu85= (c.255A>G) in the general population?

TIMP3 p.Glu85= (c.255A>G) is very rare (popmax 0.00254%, nfe) (gnomAD).

TIMP3 p.Glu85=

c.255A>G · rs373801773 · VCV593855

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00254%, 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 4	GERP 1.4, phastCons 1
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,180,024 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00186% 30/1,614,014 alleles · very rare exomes 27/1,461,868 · genomes 3/152,146 · 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.Glu85=
Coding: c.255A>G
MANE Select: NM_000362
dbSNP: rs373801773
Type: single nucleotide variant
Location: chr22:32857299 (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-glu85 (accessed [today's date]).

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