Is TRDN p.Lys445Arg (c.1334A>G) pathogenic?

TRDN p.Lys445Arg (c.1334A>G) is classified Uncertain significance in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-15). AlphaMissense: likely benign (0.1192); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Lys445Arg (c.1334A>G)?

TRDN p.Lys445Arg (c.1334A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TRDN p.Lys445Arg (c.1334A>G) in the general population?

TRDN p.Lys445Arg (c.1334A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRDN p.Lys445Arg (c.1334A>G)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

TRDN p.Lys445Arg

c.1334A>G · rs2533766076 · VCV1770212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -8.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	26.2	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

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.Lys445Arg
Coding: c.1334A>G
MANE Select: NM_006073
dbSNP: rs2533766076
Type: single nucleotide variant
Location: chr6:123352574 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 445: the 'disordered' region

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

Similar variants

TRDN p.Glu168Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Lys177Ter Pathogenic ★★ same condition
TRDN c.1166-2A>C Uncertain significance ★★ same condition
TRDN c.1273+4T>C Uncertain significance ★★ same condition
TRDN c.1273+5G>A Uncertain significance ★★ same condition
TRDN c.1322-10T>A Uncertain significance ★★ same condition
TRDN c.1537+1G>A Uncertain significance ★★ same condition
TRDN c.1597+3A>G 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/trdn-p-lys445arg (accessed [today's date]).

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