Is TNC p.Leu2002= (c.6006G>A) pathogenic?

TNC p.Leu2002= (c.6006G>A) is classified Benign/Likely benign in TNC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2022-03-15). Common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Leu2002= (c.6006G>A)?

TNC p.Leu2002= (c.6006G>A) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

TNC p.Leu2002=

Q: How common is TNC p.Leu2002= (c.6006G>A) in the general population?

TNC p.Leu2002= (c.6006G>A) is common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6006G>A · rs61736828 · VCV784149

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.19%, 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	0.081	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.077	GERP -3.2, phastCons 0.9
Overall
CADD	6.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% African / African-American · 3,893/75,028 alleles

Filtering AF 5.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5%

Overall 0.269% 4,336/1,613,776 alleles · common exomes 2,112/1,461,478 · genomes 2,224/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.19%	19
Remaining individualsnot grpmax-eligible	0.339%	295
Middle Eastern	0.297%	337
Admixed American	0.283%	353
South Asian	0.00879%	11,381
European (non-Finnish)	0.00288%	34,697
East Asian	0.00223%	44,866

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.Leu2002=
Coding: c.6006G>A
MANE Select: NM_002160
dbSNP: rs61736828
Type: single nucleotide variant
Location: chr9:115030320 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 2002: an α-helix; the fibrinogen c-terminal 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-leu2002 (accessed [today's date]).

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