Is TNC p.Arg1731= (c.5193G>A) pathogenic?

TNC p.Arg1731= (c.5193G>A) is classified Benign in TNC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-03-15). Common (popmax 5.66%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Arg1731= (c.5193G>A)?

TNC p.Arg1731= (c.5193G>A) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

TNC p.Arg1731=

Q: How common is TNC p.Arg1731= (c.5193G>A) in the general population?

TNC p.Arg1731= (c.5193G>A) is common (popmax 5.66%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5193G>A · rs61265377 · VCV776445

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.66%, 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.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -0.1
Overall
CADD	3.826	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.66% African / African-American · 4,248/75,044 alleles

Filtering AF 5.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.46%

Overall 0.313% 5,059/1,614,120 alleles · common exomes 2,666/1,461,812 · genomes 2,393/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.66%	18
Admixed American	0.418%	239
Remaining individualsnot grpmax-eligible	0.402%	249
Middle Eastern	0.396%	252
South Asian	0.0318%	3,140
European (non-Finnish)	0.0216%	4,627
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Arg1731=
Coding: c.5193G>A
MANE Select: NM_002160
dbSNP: rs61265377
Type: single nucleotide variant
Location: chr9:115042274 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 1731: the fibronectin type-iii 13 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-arg1731 (accessed [today's date]).

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