Is TNC p.Cys573= (c.1719C>T) pathogenic?

TNC p.Cys573= (c.1719C>T) is classified Benign/Likely benign in TNC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-08-21). Low-frequency (popmax 1.06%, afr); Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Cys573= (c.1719C>T)?

TNC p.Cys573= (c.1719C>T) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

How common is TNC p.Cys573= (c.1719C>T) in the general population?

TNC p.Cys573= (c.1719C>T) is low-frequency (popmax 1.06%, afr) (gnomAD).

TNC p.Cys573=

c.1719C>T · rs141544394 · VCV586833

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, afr)

Conditions

autosomal dominant nonsyndromic hearing loss 56

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5
Overall
CADD	0.343	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.06% African / African-American · 797/75,030 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.977%

Overall 0.0588% 949/1,613,844 alleles · low-frequency exomes 468/1,461,566 · genomes 481/152,278 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.06%	94
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.045%	2,221
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00712%	14,047
South Asian	0.0022%	45,514
Finnishnot grpmax-eligible	0.00156%	63,980

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.Cys573=
Coding: c.1719C>T
MANE Select: NM_002160
dbSNP: rs141544394
Type: single nucleotide variant
Location: chr9:115086012 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 573: the egf-like 14 domain; a disulfide bond

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

Disease context

autosomal dominant nonsyndromic hearing loss 56 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TNC p.Arg669His Uncertain significance ★★ ⚠ same condition
TNC p.Arg747Trp Uncertain significance ★★ ⚠ same condition
TNC p.Asp971Asn Uncertain significance ★★ ⚠ same condition
TNC p.Ile1148Val Uncertain significance ★★ ⚠ same condition
TNC p.Thr1095Ile Uncertain significance ★★ ⚠ same condition
TNC p.Thr1138Met Uncertain significance ★★ ⚠ same condition
TNC p.Thr987Met Uncertain significance ★★ ⚠ same condition
TNC p.Val1898Ile 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-cys573 (accessed [today's date]).

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