Is PDCD10 p.Arg82Cys (c.244C>T) pathogenic?

PDCD10 p.Arg82Cys (c.244C>T) is classified Uncertain significance in PDCD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: likely pathogenic (0.7402); Very rare (popmax 8.59e-05%, nfe).

How common is PDCD10 p.Arg82Cys (c.244C>T) in the general population?

PDCD10 p.Arg82Cys (c.244C>T) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

What do computational predictors say about PDCD10 p.Arg82Cys (c.244C>T)?

AlphaMissense predicts likely pathogenic (score 0.7402) — an in-silico prediction, not a clinical call.

PDCD10 p.Arg82Cys

c.244C>T · VCV4882080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7402	likely pathogenic
REVEL	0.593	indeterminate
SaProt	LLR -11.16	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.59e-05% European (non-Finnish) · 1/1,164,492 alleles

Overall 6.26e-05% 1/1,596,992 alleles · very rare exomes 1/1,444,742 · genomes 0/152,250 · joint denominator

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: PDCD10
Protein: p.Arg82Cys
Coding: c.244C>T
MANE Select: NM_007217
Type: single nucleotide variant
Location: chr3:167697033 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 82: an α-helix

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

Similar variants

PDCD10 p.Arg82fs Pathogenic ★ same residue
PDCD10 c.150+1G>A Pathogenic/Likely pathogenic ★★ same type
PDCD10 c.268+1G>A Pathogenic ★★ same type
PDCD10 c.396-2A>G Pathogenic ★★ same type
PDCD10 c.474+5G>A Pathogenic/Likely pathogenic ★★ same type
PDCD10 c.557+1G>A Pathogenic ★★ same type
PDCD10 p.Arg108Ter Pathogenic ★★ same type
PDCD10 p.Arg196Ter Pathogenic ★★ same type

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-arg82cys (accessed [today's date]).

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