Is TIMP3 p.Phe172= (c.516C>T) pathogenic?

TIMP3 p.Phe172= (c.516C>T) is classified Conflicting classifications of pathogenicity in TIMP3 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-07). Rare (popmax 0.282%, nfe); Associated with Sorsby fundus dystrophy.

What condition is associated with TIMP3 p.Phe172= (c.516C>T)?

TIMP3 p.Phe172= (c.516C>T) is associated with Sorsby fundus dystrophy (ClinVar).

How common is TIMP3 p.Phe172= (c.516C>T) in the general population?

TIMP3 p.Phe172= (c.516C>T) is rare (popmax 0.282%, nfe) (gnomAD).

How is Sorsby fundus dystrophy inherited?

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

TIMP3 p.Phe172=

c.516C>T · rs149161075 · VCV341347

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.282%, nfe)

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.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.6	GERP -3.5
Overall
CADD	8.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.282% European (non-Finnish) · 3,332/1,180,032 alleles

Filtering AF 0.274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.271%

Overall 0.221% 3,575/1,614,196 alleles · rare exomes 3,356/1,461,892 · genomes 219/152,304 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.282%	354
Admixed American	0.12%	834
Remaining individualsnot grpmax-eligible	0.117%	856
Finnishnot grpmax-eligible	0.0734%	1,362
African / African-American	0.0413%	2,421
South Asian	0.0165%	6,072
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,868
East Asian	0.00446%	22,441

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.Phe172=
Coding: c.516C>T
MANE Select: NM_000362
dbSNP: rs149161075
Type: single nucleotide variant
Location: chr22:32859257 (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-phe172 (accessed [today's date]).

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