Is PDCD5 p.Arg53Trp (c.157C>T) pathogenic?

PDCD5 p.Arg53Trp (c.157C>T) is classified Uncertain significance in PDCD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: ambiguous (0.5213); Ultra-rare (popmax 0.012%, afr).

How common is PDCD5 p.Arg53Trp (c.157C>T) in the general population?

PDCD5 p.Arg53Trp (c.157C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about PDCD5 p.Arg53Trp (c.157C>T)?

AlphaMissense predicts ambiguous (score 0.5213) — an in-silico prediction, not a clinical call.

PDCD5 p.Arg53Trp

c.157C>T · rs147553739 · VCV3210582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5213	ambiguous
REVEL	0.717	pathogenic-leaning
SaProt	LLR -14.93	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 6,035 bp · p 0.72 · regional, not allelic
Overall
CADD	28.6	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 0.012% African / African-American · 9/74,988 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00161% 26/1,613,316 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,332
Remaining individualsnot grpmax-eligible	0.0032%	31,248
East Asian	0.00223%	44,864
European (non-Finnish)	0.0011%	90,718
South Asian	0.0011%	91,060

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: PDCD5
Protein: p.Arg53Trp
Coding: c.157C>T
MANE Select: NM_004708
dbSNP: rs147553739
Type: single nucleotide variant
Location: chr19:32585002 (GRCh38)
Gene constraint: LOEUF 1.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.13 · 3 PDB
Residue 53: an α-helix

Full PDCD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD5 p.Arg53Gln Uncertain significance ★ ⚠ same residue
PDCD5 c.105-7G>A Benign ★★ same type
PDCD5 p.Glu16Lys Benign ★★ ⚠ same type
PDCD5 p.Ala27Val Uncertain significance ★ ⚠ same type
PDCD5 p.Arg10Gly Uncertain significance ★ ⚠ same type
PDCD5 p.Asp122Tyr Uncertain significance ★ ⚠ same type
PDCD5 p.Gln101Arg Uncertain significance ★ ⚠ same type
PDCD5 p.Ile93Val Uncertain significance ★ ⚠ 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/pdcd5-p-arg53trp (accessed [today's date]).

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