Is PSMD13 p.Pro259Arg (c.776C>G) pathogenic?

PSMD13 p.Pro259Arg (c.776C>G) is classified Uncertain significance in PSMD13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: ambiguous (0.3783); Absent from gnomAD v4.1.

How common is PSMD13 p.Pro259Arg (c.776C>G) in the general population?

PSMD13 p.Pro259Arg (c.776C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSMD13 p.Pro259Arg (c.776C>G)?

AlphaMissense predicts ambiguous (score 0.3783) — an in-silico prediction, not a clinical call.

PSMD13 p.Pro259Arg

c.776C>G · VCV4146537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3783	ambiguous
REVEL	0.759	pathogenic-leaning
SaProt	LLR -6.12	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.0042 · 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: PSMD13
Protein: p.Pro259Arg
Coding: c.776C>G
MANE Select: NM_002817
Type: single nucleotide variant
Location: chr11:250804 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.94 · 124 PDB
Residue 259: the pci domain; an α-helix

Full PSMD13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMD13 c.209+16C>A Uncertain significance ★ same type
PSMD13 c.209+18G>A Uncertain significance ★ same type
PSMD13 c.209+42A>C Uncertain significance ★ same type
PSMD13 c.209+43T>C Uncertain significance ★ same type
PSMD13 c.310-1G>A Uncertain significance ★ same type
PSMD13 c.397-1G>C Uncertain significance ★ same type
PSMD13 p.Arg101His Uncertain significance ★ ⚠ same type
PSMD13 p.Arg154His 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/psmd13-p-pro259arg (accessed [today's date]).

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