Is TNC p.Val902Asp (c.2705T>A) pathogenic?

TNC p.Val902Asp (c.2705T>A) is classified Uncertain significance in TNC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely pathogenic (0.6063); Ultra-rare (popmax 0.0735%, eas); Associated with Meniere disease.

What condition is associated with TNC p.Val902Asp (c.2705T>A)?

TNC p.Val902Asp (c.2705T>A) is associated with Meniere disease (ClinVar).

How common is TNC p.Val902Asp (c.2705T>A) in the general population?

TNC p.Val902Asp (c.2705T>A) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about TNC p.Val902Asp (c.2705T>A)?

AlphaMissense predicts likely pathogenic (score 0.6063) — an in-silico prediction, not a clinical call.

TNC p.Val902Asp

c.2705T>A · rs202234406 · VCV3238900

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6063 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Meniere disease

Computational evidence

Protein change
AlphaMissense	0.6063	likely pathogenic
REVEL	0.336	indeterminate
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.8 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0735% East Asian · 33/44,882 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00204% 33/1,614,200 alleles · ultra-rare exomes 32/1,461,884 · genomes 1/152,316 · joint denominator

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.Val902Asp
Coding: c.2705T>A
MANE Select: NM_002160
dbSNP: rs202234406
Type: single nucleotide variant
Location: chr9:115076545 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 902: the fibronectin type-iii 4 domain

Full TNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meniere disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TNC p.Val902Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TNC p.Arg1066Cys Likely benign ★★ ⚠ same condition
TNC p.Asp433Asn Benign ★★ same condition
TNC p.Thr710Met Uncertain significance ★ ⚠ same condition
TNC p.Glu743Lys Uncertain significance ⚠ same condition
TNC p.Gly203Val Conflicting classifications of pathogenicity ⚠ same condition
TNC p.Gly838Ser Uncertain significance ⚠ same condition
TNC p.Pro625Ser 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-val902asp (accessed [today's date]).

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