Is TRDN p.Ser339= (c.1017T>C) pathogenic?

TRDN p.Ser339= (c.1017T>C) is classified Likely benign in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 0.00136%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Ser339= (c.1017T>C)?

TRDN p.Ser339= (c.1017T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TRDN p.Ser339= (c.1017T>C) in the general population?

TRDN p.Ser339= (c.1017T>C) is very rare (popmax 0.00136%, afr) (gnomAD).

TRDN p.Ser339=

c.1017T>C · rs1774675261 · VCV2625264

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -4.9
Overall
CADD	3.981	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,404 alleles

Overall 6.28e-05% 1/1,591,736 alleles · very rare exomes 0/1,439,672 · genomes 1/152,064 · joint denominator

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: TRDN
Protein: p.Ser339=
Coding: c.1017T>C
MANE Select: NM_006073
dbSNP: rs1774675261
Type: single nucleotide variant
Location: chr6:123438097 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 339: a UniProt-annotated variant site (in); 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.Ser339Asn Benign/Likely benign ★★ same residue
TRDN p.Ser339Arg Uncertain significance ★ ⚠ same residue
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

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-ser339 (accessed [today's date]).

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