Is TOR1A p.Arg282Ter (c.844C>T) pathogenic?

TOR1A p.Arg282Ter (c.844C>T) is classified Likely pathogenic in TOR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-15). Very rare (popmax 0.0011%, sas); Associated with arthrogryposis multiplex congenita 5.

What condition is associated with TOR1A p.Arg282Ter (c.844C>T)?

TOR1A p.Arg282Ter (c.844C>T) is associated with arthrogryposis multiplex congenita 5 (ClinVar).

How common is TOR1A p.Arg282Ter (c.844C>T) in the general population?

TOR1A p.Arg282Ter (c.844C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TOR1A p.Arg282Ter

c.844C>T · rs753220814 · VCV2445982

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

arthrogryposis multiplex congenita 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -5.1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,072 alleles · very rare exomes 4/1,461,892 · genomes 0/152,180 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.000254%	393,340

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: TOR1A
Protein: p.Arg282Ter
Coding: c.844C>T
MANE Select: NM_000113
dbSNP: rs753220814
Type: single nucleotide variant
Location: chr9:129814127 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 3 PDB
Residue 282: the 'interaction with klc1' region; an α-helix

Full TOR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arthrogryposis multiplex congenita 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TOR1A p.Arg288Ter Pathogenic/Likely pathogenic ★★ same condition
TOR1A p.Leu240Ser Uncertain significance ★★ ⚠ same condition
TOR1A p.Val129Ile Uncertain significance ★★ ⚠ same condition
TOR1A p.Asp216His Benign ★★ same condition
TOR1A c.621-2A>G Likely pathogenic ★ same condition
TOR1A p.Cys162Ter Likely pathogenic ★ same condition
TOR1A p.Arg288Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
TOR1A p.Lys309Asn Likely benign ★ 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/tor1a-p-arg282ter (accessed [today's date]).

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