Is TNNT2 p.Val95= (c.285G>A) pathogenic?

TNNT2 p.Val95= (c.285G>A) is classified Likely benign in TNNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-07). Very rare (popmax 0.00167%, amr); Associated with cardiomyopathy, familial restrictive, 3.

What condition is associated with TNNT2 p.Val95= (c.285G>A)?

TNNT2 p.Val95= (c.285G>A) is associated with cardiomyopathy, familial restrictive, 3, hypertrophic cardiomyopathy 2, dilated cardiomyopathy 1D (ClinVar).

How common is TNNT2 p.Val95= (c.285G>A) in the general population?

TNNT2 p.Val95= (c.285G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

TNNT2 p.Val95=

c.285G>A · rs1060503885 · VCV412946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

cardiomyopathy, familial restrictive, 3

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 -0.14	GERP -2.7, phastCons 0.48
Overall
CADD	9.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,996 alleles

Overall 6.2e-05% 1/1,614,066 alleles · very rare exomes 1/1,461,754 · genomes 0/152,312 · 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: TNNT2
Protein: p.Val95=
Coding: c.285G>A
MANE Select: NM_001276345
dbSNP: rs1060503885
Type: single nucleotide variant
Location: chr1:201365619 (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

cardiomyopathy, familial restrictive, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 2 dilated cardiomyopathy 1D

Similar variants

TNNT2 p.Val95Met Likely pathogenic ★ same residue
TNNT2 p.Val95Ala Uncertain significance ★ ⚠ same residue
TNNT2 p.Val95Glu Uncertain significance ★ ⚠ 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-val95 (accessed [today's date]).

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