Is PDCD4 p.Arg428Trp (c.1282C>T) pathogenic?

PDCD4 p.Arg428Trp (c.1282C>T) is classified Uncertain significance in PDCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.2125); Very rare (popmax 0.00936%, afr).

How common is PDCD4 p.Arg428Trp (c.1282C>T) in the general population?

PDCD4 p.Arg428Trp (c.1282C>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about PDCD4 p.Arg428Trp (c.1282C>T)?

AlphaMissense predicts likely benign (score 0.2125) — an in-silico prediction, not a clinical call.

PDCD4 p.Arg428Trp

c.1282C>T · VCV3887139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2125	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -12.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 22 kb · p 0.31 · regional, not allelic
Overall
CADD	25.4	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 0.00936% African / African-American · 7/74,760 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00187% 30/1,608,178 alleles · very rare exomes 24/1,455,906 · genomes 6/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,680
East Asian	0.00447%	22,370
South Asian	0.0022%	45,413
European (non-Finnish)	0.00162%	61,862

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: PDCD4
Protein: p.Arg428Trp
Coding: c.1282C>T
MANE Select: NM_014456
Type: single nucleotide variant
Location: chr10:110896020 (GRCh38)
Gene constraint: LOEUF 1.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 11 PDB
Residue 428: the mi 2 domain; an α-helix

Full PDCD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD4 p.Ala118Val Uncertain significance ★ ⚠ same type
PDCD4 p.Ala84Thr Uncertain significance ★ ⚠ same type
PDCD4 p.Arg310Cys Uncertain significance ★ ⚠ same type
PDCD4 p.Arg61Thr Uncertain significance ★ ⚠ same type
PDCD4 p.Arg69Trp Uncertain significance ★ ⚠ same type
PDCD4 p.Asn410Ser Uncertain significance ★ ⚠ same type
PDCD4 p.Asp144His Uncertain significance ★ ⚠ same type
PDCD4 p.Asp246Val 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/pdcd4-p-arg428trp (accessed [today's date]).

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