Is TNC p.His52= (c.156C>T) pathogenic?

TNC p.His52= (c.156C>T) is classified Benign/Likely benign in TNC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-01). Low-frequency (popmax 1.23%, afr); Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.His52= (c.156C>T)?

TNC p.His52= (c.156C>T) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

How common is TNC p.His52= (c.156C>T) in the general population?

TNC p.His52= (c.156C>T) is low-frequency (popmax 1.23%, afr) (gnomAD).

TNC p.His52=

c.156C>T · rs7038329 · VCV786576

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -5.1
Overall
CADD	0.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.23% African / African-American · 927/75,062 alleles

Filtering AF 1.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.0851% 1,373/1,614,216 alleles · low-frequency exomes 772/1,461,894 · genomes 601/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.23%	81
Remaining individualsnot grpmax-eligible	0.088%	1,137
Admixed American	0.07%	1,429
Finnishnot grpmax-eligible	0.0578%	1,731
South Asian	0.0428%	2,336
Middle Eastern	0.033%	3,031
East Asian	0.0223%	4,489
European (non-Finnish)	0.022%	4,539
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.His52=
Coding: c.156C>T
MANE Select: NM_002160
dbSNP: rs7038329
Type: single nucleotide variant
Location: chr9:115090863 (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-his52 (accessed [today's date]).

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