Is PSMC3 p.Ile111Val (c.331A>G) pathogenic?

PSMC3 p.Ile111Val (c.331A>G) is classified Uncertain significance in PSMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely benign (0.0615); Very rare (popmax 0.00254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PSMC3 p.Ile111Val (c.331A>G)?

PSMC3 p.Ile111Val (c.331A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PSMC3 p.Ile111Val (c.331A>G) in the general population?

PSMC3 p.Ile111Val (c.331A>G) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about PSMC3 p.Ile111Val (c.331A>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

PSMC3 p.Ile111Val

c.331A>G · rs1344871576 · VCV3220402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -6.87	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 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 1,268 bp · p 2.4e-14 · regional, not allelic
Overall
CADD	20.2	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 0.00254% European (non-Finnish) · 30/1,179,894 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00192% 31/1,613,880 alleles · very rare exomes 29/1,461,758 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,330
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: PSMC3
Protein: p.Ile111Val
Coding: c.331A>G
MANE Select: NM_002804
dbSNP: rs1344871576
Type: single nucleotide variant
Location: chr11:47424666 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.58 · 139 PDB

Full PSMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSMC3 p.Ile261Thr Pathogenic ★★ same condition
PSMC3 p.His417= Likely benign ★★ same condition
PSMC3 p.Met310Thr Likely pathogenic ★ same condition
PSMC3 c.735+1G>A Uncertain significance ★ same condition
PSMC3 p.Ala18Val Uncertain significance ★ ⚠ same condition
PSMC3 p.Ala242Thr Uncertain significance ★ ⚠ same condition
PSMC3 p.Asn358Ser Uncertain significance ★ ⚠ same condition
PSMC3 p.Asn434Ser Uncertain significance ★ ⚠ 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/psmc3-p-ile111val (accessed [today's date]).

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