Is TNC p.Ala1055= (c.3165C>T) pathogenic?

TNC p.Ala1055= (c.3165C>T) is classified Benign in TNC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-03-15). Common (popmax 10.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Ala1055= (c.3165C>T)?

TNC p.Ala1055= (c.3165C>T) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

TNC p.Ala1055=

Q: How common is TNC p.Ala1055= (c.3165C>T) in the general population?

TNC p.Ala1055= (c.3165C>T) is common (popmax 10.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3165C>T · rs3748172 · VCV586834

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 10.5%, amr) — 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 -13	GERP -5.8
Overall
CADD	0.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.5% Admixed American · 6,324/60,012 alleles

Filtering AF 10.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.2%

Overall 1.22% 19,656/1,614,102 alleles · common exomes 17,166/1,461,868 · genomes 2,490/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	10.5%	9
East Asian	9.76%	10
South Asian	5.63%	18
Remaining individualsnot grpmax-eligible	1.45%	69
Finnishnot grpmax-eligible	0.881%	114
Middle Eastern	0.28%	357
African / African-American	0.239%	419
European (non-Finnish)	0.181%	553
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480

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.Ala1055=
Coding: c.3165C>T
MANE Select: NM_002160
dbSNP: rs3748172
Type: single nucleotide variant
Location: chr9:115073652 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 1055: the fibronectin type-iii 5 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.Ala1055Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala1055 (accessed [today's date]).

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