Is TNNI3K p.Ile26Val (c.76A>G) pathogenic?

TNNI3K p.Ile26Val (c.76A>G) is classified Uncertain significance in TNNI3K (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.00992%, sas); Associated with Inborn genetic diseases.

What condition is associated with TNNI3K p.Ile26Val (c.76A>G)?

TNNI3K p.Ile26Val (c.76A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TNNI3K p.Ile26Val (c.76A>G) in the general population?

TNNI3K p.Ile26Val (c.76A>G) is very rare (popmax 0.00992%, sas) (gnomAD).

What do computational predictors say about TNNI3K p.Ile26Val (c.76A>G)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

TNNI3K p.Ile26Val

c.76A>G · rs1653844095 · VCV1357020

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00992%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.18	GERP 0.35
Regional constraint	o/e 1.12	unconstrained · MANE · 309 kb · p 0.00022 · regional, not allelic
Overall
CADD	1.36	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00992% South Asian · 9/90,756 alleles

Filtering AF 0.00515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.000622% 10/1,608,348 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00992%	10,084
East Asian	0.00224%	44,598

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: TNNI3K
Protein: p.Ile26Val
Coding: c.76A>G
MANE Select: NM_015978
dbSNP: rs1653844095
Type: single nucleotide variant
Location: chr1:74236137 (GRCh38)

Full TNNI3K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/tnni3k-p-ile26val (accessed [today's date]).

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