Is PSMD12 p.Met366Val (c.1096A>G) pathogenic?

PSMD12 p.Met366Val (c.1096A>G) is classified Uncertain significance in PSMD12 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). AlphaMissense: ambiguous (0.4398); No allele count reported in gnomAD v4.1 (AN 1,576,974); Associated with Stankiewicz-Isidor syndrome.

What condition is associated with PSMD12 p.Met366Val (c.1096A>G)?

PSMD12 p.Met366Val (c.1096A>G) is associated with Stankiewicz-Isidor syndrome (ClinVar).

How common is PSMD12 p.Met366Val (c.1096A>G) in the general population?

PSMD12 p.Met366Val (c.1096A>G) is no allele count reported in gnomAD v4.1 (AN 1,576,974) (gnomAD).

What do computational predictors say about PSMD12 p.Met366Val (c.1096A>G)?

AlphaMissense predicts ambiguous (score 0.4398) — an in-silico prediction, not a clinical call.

PSMD12 p.Met366Val

c.1096A>G · rs1598552881 · VCV803461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4398 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,974)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Stankiewicz-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.4398	ambiguous
REVEL	0.26	benign-leaning
SaProt	LLR -6.40	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 7.5e-08 · regional, not allelic
Overall
CADD	21.1	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

No allele count reported in gnomAD v4.1 (AN 1,576,974). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PSMD12
Protein: p.Met366Val
Coding: c.1096A>G
MANE Select: NM_002816
dbSNP: rs1598552881
Type: single nucleotide variant
Location: chr17:67342251 (GRCh38)
Gene constraint: LOEUF 0.232 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 124 PDB
Residue 366: the pci domain; an α-helix

Full PSMD12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Stankiewicz-Isidor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSMD12 p.Arg123Ter Pathogenic ★★ same condition
PSMD12 p.Arg144Ter Pathogenic/Likely pathogenic ★★ same condition
PSMD12 p.Arg182Ter Pathogenic ★★ same condition
PSMD12 p.Asp339Glu Uncertain significance ★★ ⚠ same condition
PSMD12 p.Thr443Met Uncertain significance ★★ ⚠ same condition
PSMD12 p.Val71Leu Uncertain significance ★★ ⚠ same condition
PSMD12 c.796-3T>C Benign ★★ same condition
PSMD12 c.1084-1G>A Likely pathogenic ★ same condition

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/psmd12-p-met366val (accessed [today's date]).

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