Is TIMP3 p.Arg107= (c.321C>T) pathogenic?

TIMP3 p.Arg107= (c.321C>T) is classified Conflicting classifications of pathogenicity in TIMP3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-18). Ultra-rare (popmax 0.029%, eas); Associated with Sorsby fundus dystrophy.

What condition is associated with TIMP3 p.Arg107= (c.321C>T)?

TIMP3 p.Arg107= (c.321C>T) is associated with Sorsby fundus dystrophy (ClinVar).

How common is TIMP3 p.Arg107= (c.321C>T) in the general population?

TIMP3 p.Arg107= (c.321C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

How is Sorsby fundus dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TIMP3 p.Arg107=

c.321C>T · rs145553035 · VCV289421

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

Sorsby fundus dystrophy

⚠ 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 -11	GERP -9.6
Overall
CADD	1.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,870 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00211% 34/1,614,024 alleles · ultra-rare exomes 24/1,461,880 · genomes 10/152,144 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
African / African-American	0.0187%	5,350
South Asian	0.0022%	45,540
European (non-Finnish)	0.000424%	236,008

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.Arg107=
Coding: c.321C>T
MANE Select: NM_000362
dbSNP: rs145553035
Type: single nucleotide variant
Location: chr22:32858021 (GRCh38)

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

Disease context

Sorsby fundus dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sorsby fundus dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

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-arg107 (accessed [today's date]).

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