Is TRDN p.Arg271Gln (c.812G>A) pathogenic?

TRDN p.Arg271Gln (c.812G>A) is classified Uncertain significance in TRDN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-19). AlphaMissense: ambiguous (0.3679); Ultra-rare (popmax 0.0168%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Arg271Gln (c.812G>A)?

TRDN p.Arg271Gln (c.812G>A) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Arg271Gln (c.812G>A) in the general population?

TRDN p.Arg271Gln (c.812G>A) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about TRDN p.Arg271Gln (c.812G>A)?

AlphaMissense predicts ambiguous (score 0.3679) — an in-silico prediction, not a clinical call.

TRDN p.Arg271Gln

c.812G>A · rs772783444 · VCV519526

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3679	ambiguous
REVEL	0.249	benign-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.32	acceptor loss · deltas
Pangolin	Δ0.41	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	28.8	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 0.0168% Middle Eastern · 1/5,958 alleles

Filtering AF 0.000439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00032%

Overall 0.000901% 14/1,553,814 alleles · ultra-rare exomes 13/1,401,804 · genomes 1/152,010 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,958
East Asian	0.0024%	41,598
Admixed American	0.00201%	49,834
African / African-American	0.00139%	72,128
European (non-Finnish)	0.000869%	115,106

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.Arg271Gln
Coding: c.812G>A
MANE Select: NM_006073
dbSNP: rs772783444
Type: single nucleotide variant
Location: chr6:123497234 (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

Similar variants

TRDN p.Arg271Ter Uncertain significance ★★ same residue
TRDN p.Arg271Pro Uncertain significance ★ ⚠ same residue
TRDN p.Glu271Lys 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

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-arg271gln (accessed [today's date]).

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