Is PSMC3IP p.Phe72Ser (c.215T>C) pathogenic?

PSMC3IP p.Phe72Ser (c.215T>C) is classified Pathogenic in PSMC3IP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-06-02). AlphaMissense: likely pathogenic (0.8879); Very rare (popmax 8.47e-05%, nfe); Associated with ovarian dysgenesis 3.

What condition is associated with PSMC3IP p.Phe72Ser (c.215T>C)?

PSMC3IP p.Phe72Ser (c.215T>C) is associated with ovarian dysgenesis 3 (ClinVar).

How common is PSMC3IP p.Phe72Ser (c.215T>C) in the general population?

PSMC3IP p.Phe72Ser (c.215T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PSMC3IP p.Phe72Ser (c.215T>C)?

AlphaMissense predicts likely pathogenic (score 0.8879) — an in-silico prediction, not a clinical call.

PSMC3IP p.Phe72Ser

c.215T>C · VCV3901240

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ovarian dysgenesis 3

Computational evidence

Protein change
AlphaMissense	0.8879	likely pathogenic ✓ concordant with ClinVar · top 6% in PSMC3IP
REVEL	0.401	indeterminate
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,715 bp · p 0.42 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.2e-05% 1/1,613,986 alleles · very rare exomes 1/1,461,868 · genomes 0/152,118 · 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.Phe72Ser
Coding: c.215T>C
MANE Select: NM_016556
Type: single nucleotide variant
Location: chr17:42577223 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.45

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

Disease context

ovarian dysgenesis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSMC3IP c.338-15C>G Benign ★★ same condition
PSMC3IP c.-35C>T Uncertain significance ★ same condition
PSMC3IP p.Lys63Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
PSMC3IP c.597+1G-T Pathogenic same condition
PSMC3IP p.Lys69del Likely pathogenic ★ 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

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-phe72ser (accessed [today's date]).

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