Is PSMC3IP p.Glu136= (c.408A>G) pathogenic?

PSMC3IP p.Glu136= (c.408A>G) is classified Likely benign in PSMC3IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). Very rare (popmax 0.004%, afr).

How common is PSMC3IP p.Glu136= (c.408A>G) in the general population?

PSMC3IP p.Glu136= (c.408A>G) is very rare (popmax 0.004%, afr) (gnomAD).

PSMC3IP p.Glu136=

c.408A>G · VCV3694620

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -2	GERP -5.5
Overall
CADD	3.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,072 alleles · very rare exomes 0/1,461,858 · genomes 3/152,214 · joint denominator

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.Glu136=
Coding: c.408A>G
MANE Select: NM_016556
Type: single nucleotide variant
Location: chr17:42573553 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.45
Residue 136: the 'dna-binding' region

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

Similar variants

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
PSMC3IP c.338-15C>G 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-glu136 (accessed [today's date]).

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