Is PDCD4 p.Gln322Arg (c.965A>G) pathogenic?

PDCD4 p.Gln322Arg (c.965A>G) is classified Uncertain significance in PDCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1008); Ultra-rare (popmax 0.0262%, nfe).

How common is PDCD4 p.Gln322Arg (c.965A>G) in the general population?

PDCD4 p.Gln322Arg (c.965A>G) is ultra-rare (popmax 0.0262%, nfe) (gnomAD).

What do computational predictors say about PDCD4 p.Gln322Arg (c.965A>G)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

PDCD4 p.Gln322Arg

c.965A>G · rs143809858 · VCV2240463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0262%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -0.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 22 kb · p 0.31 · regional, not allelic
Overall
CADD	15.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0262% European (non-Finnish) · 308/1,176,052 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0228%

Overall 0.0204% 328/1,609,360 alleles · ultra-rare exomes 310/1,457,198 · genomes 18/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0262%	3,818
Remaining individualsnot grpmax-eligible	0.0161%	6,230
African / African-American	0.012%	8,316
Admixed American	0.00167%	59,958

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.Gln322Arg
Coding: c.965A>G
MANE Select: NM_014456
dbSNP: rs143809858
Type: single nucleotide variant
Location: chr10:110890645 (GRCh38)
Gene constraint: LOEUF 1.671 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 11 PDB

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

Similar variants

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PDCD4 p.Arg310Cys Uncertain significance ★ ⚠ same type
PDCD4 p.Arg428Trp 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

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-gln322arg (accessed [today's date]).

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