Is PDCD10 p.Arg158Ser (c.474G>T) pathogenic?

PDCD10 p.Arg158Ser (c.474G>T) is classified Uncertain significance in PDCD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-14). AlphaMissense: likely pathogenic (0.9715); Absent from gnomAD v4.1.

How common is PDCD10 p.Arg158Ser (c.474G>T) in the general population?

PDCD10 p.Arg158Ser (c.474G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD10 p.Arg158Ser (c.474G>T)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

PDCD10 p.Arg158Ser

c.474G>T · rs2108375013 · VCV1313458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic
REVEL	0.207	benign-leaning
SaProt	LLR -4.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDCD10
Protein: p.Arg158Ser
Coding: c.474G>T
MANE Select: NM_007217
dbSNP: rs2108375013
Type: single nucleotide variant
Location: chr3:167687615 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 158: an α-helix

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

Similar variants

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
PDCD10 p.Arg35Ter 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-arg158ser (accessed [today's date]).

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