Is TNC p.Ile830= (c.2490C>T) pathogenic?

TNC p.Ile830= (c.2490C>T) is classified Benign/Likely benign in TNC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-08). Rare (popmax 0.277%, afr); Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Ile830= (c.2490C>T)?

TNC p.Ile830= (c.2490C>T) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

How common is TNC p.Ile830= (c.2490C>T) in the general population?

TNC p.Ile830= (c.2490C>T) is rare (popmax 0.277%, afr) (gnomAD).

TNC p.Ile830=

c.2490C>T · rs145321605 · VCV735144

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.277%, 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 -3.8	GERP -5.6
Overall
CADD	1.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.277% African / African-American · 208/75,054 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.234%

Overall 0.0144% 233/1,614,146 alleles · rare exomes 112/1,461,852 · genomes 121/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.277%	361
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00333%	30,011
European (non-Finnish)	0.0011%	90,770

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.Ile830=
Coding: c.2490C>T
MANE Select: NM_002160
dbSNP: rs145321605
Type: single nucleotide variant
Location: chr9:115078127 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 830: the fibronectin type-iii 3 domain

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-ile830 (accessed [today's date]).

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