Is TTN p.Val15744Ile (c.47230G>A) pathogenic?

TTN p.Val15744Ile (c.47230G>A) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-23). AlphaMissense: likely benign (0.091); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Val15744Ile (c.47230G>A)?

TTN p.Val15744Ile (c.47230G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is TTN p.Val15744Ile (c.47230G>A) in the general population?

TTN p.Val15744Ile (c.47230G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTN p.Val15744Ile (c.47230G>A)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

TTN p.Val15744Ile

c.47230G>A · rs2470892849 · VCV1784273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 6.3e-14 · regional, not allelic
Overall
CADD	20.8	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V14103I vs ClinVar V15744I) — verify the residue.

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: TTN
Protein: p.Val15744Ile
Coding: c.47230G>A
MANE Select: NM_001267550
dbSNP: rs2470892849
Type: single nucleotide variant
Location: chr2:178618228 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 15744: the fibronectin type-iii 14 domain

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

Disease context

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

Similar variants

TTN p.Val15744= Likely benign ★ same residue
TTN c.107377+1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.54190+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.54811+1G>A Likely pathogenic ★★ same condition
TTN c.57112-1G>A Likely pathogenic ★★ same condition
TTN c.58732+2T>C Likely pathogenic ★★ same condition
TTN c.95723-2A>C Likely pathogenic ★★ same condition
TTN p.Arg1012Ter Pathogenic/Likely pathogenic ★★ 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/ttn-p-val15744ile (accessed [today's date]).

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