Is TRDN p.Phe277Val (c.829T>G) pathogenic?

TRDN p.Phe277Val (c.829T>G) is classified Uncertain significance in TRDN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.8495); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Phe277Val (c.829T>G)?

TRDN p.Phe277Val (c.829T>G) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Phe277Val (c.829T>G) in the general population?

TRDN p.Phe277Val (c.829T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRDN p.Phe277Val (c.829T>G)?

AlphaMissense predicts likely pathogenic (score 0.8495) — an in-silico prediction, not a clinical call.

TRDN p.Phe277Val

c.829T>G · rs2534274767 · VCV2038907

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8495 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8495	likely pathogenic · top 5% in TRDN
REVEL	0.271	benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

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: TRDN
Protein: p.Phe277Val
Coding: c.829T>G
MANE Select: NM_006073
dbSNP: rs2534274767
Type: single nucleotide variant
Location: chr6:123497217 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65

Full TRDN 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

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

Similar variants

TRDN c.22+1G>T Pathogenic ★★ same condition
TRDN c.22+29A>G Pathogenic ★★ same condition
TRDN c.391+1G>A Likely pathogenic ★★ same condition
TRDN p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Glu168Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Glu181Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Lys177Ter Pathogenic ★★ same condition
TRDN p.Met1Thr 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/trdn-p-phe277val (accessed [today's date]).

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