Is PSMD3 p.Pro28Leu (c.83C>T) pathogenic?

PSMD3 p.Pro28Leu (c.83C>T) is classified Likely benign in PSMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely benign (0.0692); Very rare (popmax 8.72e-05%, nfe).

How common is PSMD3 p.Pro28Leu (c.83C>T) in the general population?

PSMD3 p.Pro28Leu (c.83C>T) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

What do computational predictors say about PSMD3 p.Pro28Leu (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

PSMD3 p.Pro28Leu

c.83C>T · rs1026627350 · VCV2249630

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -9.02	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 1.6	GERP -3.3, phastCons 0.69
Regional constraint	o/e 0.83	unconstrained · MANE · 14 kb · p 0.00025 · regional, not allelic
Overall
CADD	15.83	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 8.72e-05% European (non-Finnish) · 1/1,146,696 alleles

Overall 7.16e-05% 1/1,397,506 alleles · very rare

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: PSMD3
Protein: p.Pro28Leu
Coding: c.83C>T
MANE Select: NM_002809
dbSNP: rs1026627350
Type: single nucleotide variant
Location: chr17:39981053 (GRCh38)
Gene constraint: LOEUF 0.171 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.25 · 124 PDB
Residue 28: the 'disordered' region

Full PSMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMD3 p.Val227= Benign ★★ same type
PSMD3 p.Ala155Val Uncertain significance ★ ⚠ same type
PSMD3 p.Ala15Gly Uncertain significance ★ ⚠ same type
PSMD3 p.Ala215Thr Uncertain significance ★ ⚠ same type
PSMD3 p.Ala312Thr Uncertain significance ★ ⚠ same type
PSMD3 p.Ala41Pro Uncertain significance ★ ⚠ same type
PSMD3 p.Arg106His Uncertain significance ★ ⚠ same type
PSMD3 p.Arg107Cys 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/psmd3-p-pro28leu (accessed [today's date]).

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