Is PSMD3 p.Thr151Met (c.452C>T) pathogenic?

PSMD3 p.Thr151Met (c.452C>T) is classified Uncertain significance in PSMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1653); Very rare (popmax 0.005%, amr).

How common is PSMD3 p.Thr151Met (c.452C>T) in the general population?

PSMD3 p.Thr151Met (c.452C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PSMD3 p.Thr151Met (c.452C>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

PSMD3 p.Thr151Met

c.452C>T · VCV4573331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 14 kb · p 0.00025 · regional, not allelic
Overall
CADD	22.5	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 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000991% 16/1,614,034 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
South Asian	0.0011%	91,088
European (non-Finnish)	0.00102%	98,336

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.Thr151Met
Coding: c.452C>T
MANE Select: NM_002809
Type: single nucleotide variant
Location: chr17:39986615 (GRCh38)
Gene constraint: LOEUF 0.171 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.25 · 124 PDB
Residue 151: an α-helix

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-thr151met (accessed [today's date]).

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