Is TNNT2 p.Val95Ala (c.284T>C) pathogenic?

TNNT2 p.Val95Ala (c.284T>C) is classified Uncertain significance in TNNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-17). AlphaMissense: likely pathogenic (0.9301); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1D.

What condition is associated with TNNT2 p.Val95Ala (c.284T>C)?

TNNT2 p.Val95Ala (c.284T>C) is associated with dilated cardiomyopathy 1D, hypertrophic cardiomyopathy 2, cardiomyopathy, familial restrictive, 3 (ClinVar).

How common is TNNT2 p.Val95Ala (c.284T>C) in the general population?

TNNT2 p.Val95Ala (c.284T>C) is absent from gnomAD v4.1 (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TNNT2 p.Val95Ala (c.284T>C)?

AlphaMissense predicts likely pathogenic (score 0.9301) — an in-silico prediction, not a clinical call.

TNNT2 p.Val95Ala

c.284T>C · rs2102264743 · VCV1396943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1D

Computational evidence

Protein change
AlphaMissense	0.9301	likely pathogenic
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -11.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 14 kb · p 4.5e-08 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TNNT2
Protein: p.Val95Ala
Coding: c.284T>C
MANE Select: NM_001276345
dbSNP: rs2102264743
Type: single nucleotide variant
Location: chr1:201365620 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93 · 25 PDB
Residue 95: the 'disordered' region

Full TNNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 2 cardiomyopathy, familial restrictive, 3

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

TNNT2 p.Val95Met Likely pathogenic ★ same residue
TNNT2 p.Val95Glu Uncertain significance ★ ⚠ same residue
TNNT2 p.Val95= Likely benign ★ same residue
TNNT2 p.Val95fs Uncertain significance ★★ same residue
TNNT2 c.851+1G>A Likely pathogenic ★★★ same condition
TNNT2 p.Arg104His Likely pathogenic ★★★ same condition
TNNT2 p.Trp297Ter Likely pathogenic ★★★ same condition
TNNT2 p.Arg296Cys 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/tnnt2-p-val95ala (accessed [today's date]).

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