Is TNC p.Tyr869= (c.2607C>T) pathogenic?

TNC p.Tyr869= (c.2607C>T) is classified Likely benign in TNC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Ultra-rare (popmax 0.0213%, afr); Associated with TNC-related disorder.

What condition is associated with TNC p.Tyr869= (c.2607C>T)?

TNC p.Tyr869= (c.2607C>T) is associated with TNC-related disorder (ClinVar).

How common is TNC p.Tyr869= (c.2607C>T) in the general population?

TNC p.Tyr869= (c.2607C>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

TNC p.Tyr869=

c.2607C>T · rs143668894 · VCV3049502

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Conditions

TNC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.3	GERP -5.6
Overall
CADD	0.535	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/74,942 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0088% 142/1,614,112 alleles · ultra-rare exomes 129/1,461,890 · genomes 13/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,684
South Asian	0.0154%	6,506
European (non-Finnish)	0.00915%	10,926
Remaining individualsnot grpmax-eligible	0.0048%	20,830
Admixed American	0.00167%	60,014

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: TNC
Protein: p.Tyr869=
Coding: c.2607C>T
MANE Select: NM_002160
dbSNP: rs143668894
Type: single nucleotide variant
Location: chr9:115078010 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 869: a β-strand; the fibronectin type-iii 3 domain

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

Disease context

TNC-related disorder

Similar variants

TNC p.Tyr869Asn Uncertain significance ★ ⚠ same residue
TNC p.Asp520Asn Uncertain significance ★ ⚠ same condition
TNC p.Gly493Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
TNC p.Ser760Gly Uncertain significance ★ ⚠ same condition
TNC p.Val902Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
TNC p.Ala115Thr Uncertain significance ⚠ same condition
TNC p.Asn410Ser Uncertain significance ⚠ same condition
TNC p.Glu1297Lys Uncertain significance ⚠ same condition

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/tnc-p-tyr869 (accessed [today's date]).

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