Is TNC p.Lys32= (c.96G>A) pathogenic?

TNC p.Lys32= (c.96G>A) is classified Benign/Likely benign in TNC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-11-23). Rare (popmax 0.716%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Lys32= (c.96G>A)?

TNC p.Lys32= (c.96G>A) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

How common is TNC p.Lys32= (c.96G>A) in the general population?

TNC p.Lys32= (c.96G>A) is rare (popmax 0.716%, nfe) (gnomAD).

TNC p.Lys32=

c.96G>A · rs145367019 · VCV776765

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.716%, nfe)

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 0.035	GERP -1.2, phastCons 0.83
Overall
CADD	8.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.716% European (non-Finnish) · 8,447/1,180,040 alleles

Filtering AF 0.703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.698%

Overall 0.566% 9,132/1,614,174 alleles · rare exomes 8,547/1,461,888 · genomes 585/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.716%	140
Remaining individualsnot grpmax-eligible	0.408%	245
Admixed American	0.285%	351
South Asian	0.142%	706
African / African-American	0.103%	974
Middle Eastern	0.099%	1,010
Finnishnot grpmax-eligible	0.0672%	1,489
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402

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.Lys32=
Coding: c.96G>A
MANE Select: NM_002160
dbSNP: rs145367019
Type: single nucleotide variant
Location: chr9:115090923 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB

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-lys32 (accessed [today's date]).

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