Is PSMD2 p.Ser29Arg (c.87C>A) pathogenic?

PSMD2 p.Ser29Arg (c.87C>A) is classified Uncertain significance in PSMD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely benign (0.2202); Very rare (popmax 0.00145%, sas).

How common is PSMD2 p.Ser29Arg (c.87C>A) in the general population?

PSMD2 p.Ser29Arg (c.87C>A) is very rare (popmax 0.00145%, sas) (gnomAD).

What do computational predictors say about PSMD2 p.Ser29Arg (c.87C>A)?

AlphaMissense predicts likely benign (score 0.2202) — an in-silico prediction, not a clinical call.

PSMD2 p.Ser29Arg

c.87C>A · rs1161247727 · VCV2280539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00145%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2202	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.26	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 0.062	GERP -2, phastCons 0.89
Regional constraint	o/e 1.07	unconstrained · MANE · 2,320 bp · p 0.31 · regional, not allelic
Overall
CADD	16.8	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 0.00145% South Asian · 1/68,974 alleles

Filtering AF 0.000317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000229%

Overall 0.000637% 9/1,411,814 alleles · very rare exomes 9/1,259,532 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00145%	68,974
European (non-Finnish)	0.000736%	135,783

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: PSMD2
Protein: p.Ser29Arg
Coding: c.87C>A
MANE Select: NM_002808
dbSNP: rs1161247727
Type: single nucleotide variant
Location: chr3:184299353 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.98 · 129 PDB
Residue 29: a modified residue (phosphoserine); the 'disordered' region

Full PSMD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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PSMD2 p.Ala642Thr Uncertain significance ★ ⚠ same type
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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/psmd2-p-ser29arg (accessed [today's date]).

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