Is TNC p.Arg797= (c.2389A>C) pathogenic?

TNC p.Arg797= (c.2389A>C) is classified Benign in TNC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-04-17). Common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Arg797= (c.2389A>C)?

TNC p.Arg797= (c.2389A>C) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

TNC p.Arg797=

Q: How common is TNC p.Arg797= (c.2389A>C) in the general population?

TNC p.Arg797= (c.2389A>C) is common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2389A>C · rs16932195 · VCV805675

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele

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 6.1	GERP 2.9, phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.5% African / African-American · 8,618/74,970 alleles

Filtering AF 11.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.2%

Overall 0.598% 9,647/1,613,964 alleles · common exomes 4,741/1,461,664 · genomes 4,906/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.5%	9
Remaining individualsnot grpmax-eligible	0.765%	131
Admixed American	0.683%	146
Middle Eastern	0.35%	286
South Asian	0.0187%	5,358
European (non-Finnish)	0.00856%	11,683
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,884

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.Arg797=
Coding: c.2389A>C
MANE Select: NM_002160
dbSNP: rs16932195
Type: single nucleotide variant
Location: chr9:115081787 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 797: the fibronectin type-iii 2 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-arg797 (accessed [today's date]).

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