Is TNC p.Asp575= (c.1725C>T) pathogenic?

TNC p.Asp575= (c.1725C>T) is classified Likely benign in TNC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-01). Very rare (popmax 0.00446%, eas); Associated with TNC-related disorder.

What condition is associated with TNC p.Asp575= (c.1725C>T)?

TNC p.Asp575= (c.1725C>T) is associated with TNC-related disorder (ClinVar).

How common is TNC p.Asp575= (c.1725C>T) in the general population?

TNC p.Asp575= (c.1725C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

TNC p.Asp575=

c.1725C>T · VCV3355632

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -9.2
Overall
CADD	0.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00136% 22/1,613,870 alleles · very rare exomes 21/1,461,528 · genomes 1/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.00144%	69,406
African / African-American	0.00133%	75,050
South Asian	0.0011%	91,024

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.Asp575=
Coding: c.1725C>T
MANE Select: NM_002160
Type: single nucleotide variant
Location: chr9:115086006 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 575: the egf-like 14 domain

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

Disease context

TNC-related disorder

Similar variants

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
TNC p.Gly203Val Conflicting classifications of pathogenicity ⚠ 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-asp575 (accessed [today's date]).

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