Is TRDN p.Pro511Thr (c.1531C>A) pathogenic?

TRDN p.Pro511Thr (c.1531C>A) is classified Benign/Likely benign in TRDN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0599); Rare (popmax 0.628%, afr); Associated with Cardiovascular phenotype.

How common is TRDN p.Pro511Thr (c.1531C>A) in the general population?

TRDN p.Pro511Thr (c.1531C>A) is rare (popmax 0.628%, afr) (gnomAD).

What do computational predictors say about TRDN p.Pro511Thr (c.1531C>A)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

TRDN p.Pro511Thr

Q: What condition is associated with TRDN p.Pro511Thr (c.1531C>A)?

TRDN p.Pro511Thr (c.1531C>A) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 5 (ClinVar).

c.1531C>A · rs146935076 · VCV415178

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.628%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.13, phastCons 0.48
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	19.79	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 0.628% African / African-American · 470/74,866 alleles

Filtering AF 0.581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.562%

Overall 0.0318% 511/1,608,382 alleles · rare exomes 258/1,456,250 · genomes 253/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.628%	159
Middle Eastern	0.0344%	2,910
Remaining individualsnot grpmax-eligible	0.0337%	2,963
Admixed American	0.0235%	4,261
South Asian	0.00111%	90,104
European (non-Finnish)	0.000255%	392,489

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.Pro511Thr
Coding: c.1531C>A
MANE Select: NM_006073
dbSNP: rs146935076
Type: single nucleotide variant
Location: chr6:123279062 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 511: 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

Also linked: catecholaminergic polymorphic ventricular tachycardia 1 catecholaminergic polymorphic ventricular tachycardia 5

Similar variants

TRDN p.Pro511= Likely benign ★ same residue
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

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-pro511thr (accessed [today's date]).

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