Is TNC p.Val232= (c.696A>G) pathogenic?

TNC p.Val232= (c.696A>G) is classified Benign in TNC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-09-10). Common (popmax 57.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal dominant nonsyndromic hearing loss 56.

What condition is associated with TNC p.Val232= (c.696A>G)?

TNC p.Val232= (c.696A>G) is associated with autosomal dominant nonsyndromic hearing loss 56 (ClinVar).

TNC p.Val232=

Q: How common is TNC p.Val232= (c.696A>G) in the general population?

TNC p.Val232= (c.696A>G) is common (popmax 57.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.696A>G · rs2992147 · VCV1280191

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 57.8%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	phastCons 0.002
Overall
CADD	6.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.8% African / African-American · 43,354/74,960 alleles

Filtering AF 57.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.2%

Overall 44% 709,574/1,613,822 alleles · common exomes 637,220/1,461,822 · genomes 72,354/152,000 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	57.8%	2
Admixed American	56.4%	2
Ashkenazi Jewishnot grpmax-eligible	54.9%	2
Middle Eastern	46.1%	2
Remaining individualsnot grpmax-eligible	44.2%	2
Finnishnot grpmax-eligible	43.6%	2
European (non-Finnish)	43.2%	2
South Asian	38.5%	3
Amishnot grpmax-eligible	38.3%	3
East Asian	29.1%	3

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.Val232=
Coding: c.696A>G
MANE Select: NM_002160
dbSNP: rs2992147
Type: single nucleotide variant
Location: chr9:115087035 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 232: the egf-like 3 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-val232 (accessed [today's date]).

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