Is TTN p.Asp17153Glu (c.51459T>G) pathogenic?

TTN p.Asp17153Glu (c.51459T>G) is classified Uncertain significance in TTN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-01). AlphaMissense: likely benign (0.2793); Ultra-rare (popmax 0.0201%, eas); Associated with cardiomyopathy.

What condition is associated with TTN p.Asp17153Glu (c.51459T>G)?

TTN p.Asp17153Glu (c.51459T>G) is associated with cardiomyopathy (ClinVar).

How common is TTN p.Asp17153Glu (c.51459T>G) in the general population?

TTN p.Asp17153Glu (c.51459T>G) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about TTN p.Asp17153Glu (c.51459T>G)?

AlphaMissense predicts likely benign (score 0.2793) — an in-silico prediction, not a clinical call.

TTN p.Asp17153Glu

c.51459T>G · rs151281257 · VCV2438391

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.2793	likely benign
REVEL	0.205	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 1.6	GERP -4.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 6.3e-14 · regional, not allelic
Overall
CADD	14.17	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 D15512E vs ClinVar D17153E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,704 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00782%

Overall 0.00366% 59/1,612,134 alleles · ultra-rare exomes 54/1,460,066 · genomes 5/152,068 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,967
South Asian	0.0143%	6,994
Remaining individualsnot grpmax-eligible	0.0032%	31,202
European (non-Finnish)	0.00297%	33,685

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: TTN
Protein: p.Asp17153Glu
Coding: c.51459T>G
MANE Select: NM_001267550
dbSNP: rs151281257
Type: single nucleotide variant
Location: chr2:178609964 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

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

Disease context

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

Similar variants

TTN p.Asp17153fs Pathogenic/Likely pathogenic ★★ same residue
TTN p.Asp17153= Likely benign ★ same residue
TTN c.2775+1G>T Likely pathogenic ★★ same condition
TTN c.54811+1G>A Likely pathogenic ★★ same condition
TTN c.58732+2T>C Likely pathogenic ★★ same condition
TTN c.67349-2A>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.86821+2T>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.97492+1G>C 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-asp17153glu (accessed [today's date]).

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