Is PDCD10 p.Arg196Ter (c.586C>T) pathogenic?

PDCD10 p.Arg196Ter (c.586C>T) is classified Pathogenic in PDCD10 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-06-20). No allele count reported in gnomAD v4.1 (AN 1,606,252); Associated with PDCD10-related disorder.

What condition is associated with PDCD10 p.Arg196Ter (c.586C>T)?

PDCD10 p.Arg196Ter (c.586C>T) is associated with PDCD10-related disorder, cerebral cavernous malformation 3 (ClinVar).

How common is PDCD10 p.Arg196Ter (c.586C>T) in the general population?

PDCD10 p.Arg196Ter (c.586C>T) is no allele count reported in gnomAD v4.1 (AN 1,606,252) (gnomAD).

PDCD10 p.Arg196Ter

c.586C>T · rs1404676956 · VCV590684

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,252)

Conditions

PDCD10-related disorder

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 (9 of 9) — 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 7.5	GERP 2.4, phastCons 1
Overall
CADD	41.0	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

No allele count reported in gnomAD v4.1 (AN 1,606,252). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDCD10
Protein: p.Arg196Ter
Coding: c.586C>T
MANE Select: NM_007217
dbSNP: rs1404676956
Type: single nucleotide variant
Location: chr3:167684361 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 196: an α-helix

Full PDCD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PDCD10-related disorder

Also linked: cerebral cavernous malformation 3

Similar variants

PDCD10 p.Arg196Gln Uncertain significance ★★ ⚠ same residue
PDCD10 c.396-2A>G Pathogenic ★★ same condition
PDCD10 c.474+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDCD10 c.557+1G>A Pathogenic ★★ same condition
PDCD10 p.Arg108Ter Pathogenic ★★ same condition
PDCD10 p.Arg35Ter Pathogenic ★★ same condition
PDCD10 p.Arg95Ter Pathogenic ★★ same condition
PDCD10 p.Glu140Ter 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/pdcd10-p-arg196ter (accessed [today's date]).

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