Is TRDN p.Phe107Val (c.319T>G) pathogenic?

TRDN p.Phe107Val (c.319T>G) is classified Uncertain significance in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.3456); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Phe107Val (c.319T>G)?

TRDN p.Phe107Val (c.319T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TRDN p.Phe107Val (c.319T>G) in the general population?

TRDN p.Phe107Val (c.319T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRDN p.Phe107Val (c.319T>G)?

AlphaMissense predicts ambiguous (score 0.3456) — an in-silico prediction, not a clinical call.

TRDN p.Phe107Val

c.319T>G · VCV3461007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3456 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3456	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -6.58	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	22.6	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.Phe107Val
Coding: c.319T>G
MANE Select: NM_006073
Type: single nucleotide variant
Location: chr6:123548526 (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

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-phe107val (accessed [today's date]).

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