Is TRDN p.Ser80Phe (c.239C>T) pathogenic?

TRDN p.Ser80Phe (c.239C>T) is classified Conflicting classifications of pathogenicity in TRDN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely pathogenic (0.7873); Rare (popmax 0.249%, amr); Associated with Cardiovascular phenotype.

How common is TRDN p.Ser80Phe (c.239C>T) in the general population?

TRDN p.Ser80Phe (c.239C>T) is rare (popmax 0.249%, amr) (gnomAD).

What do computational predictors say about TRDN p.Ser80Phe (c.239C>T)?

AlphaMissense predicts likely pathogenic (score 0.7873) — an in-silico prediction, not a clinical call.

TRDN p.Ser80Phe

Q: What condition is associated with TRDN p.Ser80Phe (c.239C>T)?

TRDN p.Ser80Phe (c.239C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 5 (ClinVar).

c.239C>T · rs181287533 · VCV449704

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7873 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.249%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7873	likely pathogenic · top 7% in TRDN
REVEL	0.341	indeterminate
SaProt	LLR -9.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.249% Admixed American · 75/30,084 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.00585% 82/1,401,120 alleles · rare exomes 59/1,257,372 · genomes 23/143,748 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.249%	401
Remaining individualsnot grpmax-eligible	0.00941%	10,625
African / African-American	0.00314%	31,811

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.Ser80Phe
Coding: c.239C>T
MANE Select: NM_006073
dbSNP: rs181287533
Type: single nucleotide variant
Location: chr6:123548606 (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 catecholaminergic polymorphic ventricular tachycardia 5

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-ser80phe (accessed [today's date]).

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