Is PDS5B p.Pro1284Arg (c.3851C>G) pathogenic?

PDS5B p.Pro1284Arg (c.3851C>G) is classified Uncertain significance in PDS5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely pathogenic (0.7849); Absent from gnomAD v4.1.

How common is PDS5B p.Pro1284Arg (c.3851C>G) in the general population?

PDS5B p.Pro1284Arg (c.3851C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDS5B p.Pro1284Arg (c.3851C>G)?

AlphaMissense predicts likely pathogenic (score 0.7849) — an in-silico prediction, not a clinical call.

PDS5B p.Pro1284Arg

c.3851C>G · VCV3887552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7849 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7849	likely pathogenic
REVEL	0.245	benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.14 · regional, not allelic
Overall
CADD	26.1	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: PDS5B
Protein: p.Pro1284Arg
Coding: c.3851C>G
MANE Select: NM_015032
Type: single nucleotide variant
Location: chr13:32770347 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 1 PDB
Residue 1284: the 'disordered' region

Full PDS5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDS5B p.Pro1284Leu Uncertain significance ★ ⚠ same residue
PDS5B p.Asn284= Benign ★★ same type
PDS5B p.Asp1202= Benign ★★ same type
PDS5B c.625-1G>C Uncertain significance ★ same type
PDS5B p.Ala1399Gly Uncertain significance ★ ⚠ same type
PDS5B p.Ala1399Thr Uncertain significance ★ ⚠ same type
PDS5B p.Ala520Val Uncertain significance ★ ⚠ same type
PDS5B p.Ala576Ser 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/pds5b-p-pro1284arg (accessed [today's date]).

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