Is PSMC3IP p.Cys137= (c.411C>T) pathogenic?

PSMC3IP p.Cys137= (c.411C>T) is classified Likely benign in PSMC3IP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-18). Ultra-rare (popmax 0.036%, afr); Associated with PSMC3IP-related disorder.

What condition is associated with PSMC3IP p.Cys137= (c.411C>T)?

PSMC3IP p.Cys137= (c.411C>T) is associated with PSMC3IP-related disorder (ClinVar).

How common is PSMC3IP p.Cys137= (c.411C>T) in the general population?

PSMC3IP p.Cys137= (c.411C>T) is ultra-rare (popmax 0.036%, afr) (gnomAD).

PSMC3IP p.Cys137=

c.411C>T · rs149332082 · VCV3034321

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Conditions

PSMC3IP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.6, phastCons 0.99
Overall
CADD	9.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.036% African / African-American · 27/75,016 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00372% 60/1,614,096 alleles · ultra-rare exomes 46/1,461,824 · genomes 14/152,272 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,778
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0112%	8,928
Admixed American	0.00333%	30,010
European (non-Finnish)	0.00186%	53,635

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: PSMC3IP
Protein: p.Cys137=
Coding: c.411C>T
MANE Select: NM_016556
dbSNP: rs149332082
Type: single nucleotide variant
Location: chr17:42573550 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.45
Residue 137: the 'dna-binding' region

Full PSMC3IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PSMC3IP-related disorder

Similar variants

PSMC3IP p.Arg25Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
PSMC3IP p.Glu160Lys Uncertain significance ★★ ⚠ same type
PSMC3IP c.136-10C>T Benign ★★ same type
PSMC3IP c.225+79G>A Benign ★★ same type
PSMC3IP c.225+89C>T Likely benign ★★ same type
PSMC3IP c.337+88C>T Benign ★★ same type
PSMC3IP c.338-147T>C Benign ★★ same type
PSMC3IP c.338-158G>A Benign ★★ 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/psmc3ip-p-cys137 (accessed [today's date]).

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