Is PSMC3IP p.Arg5Pro (c.14G>C) pathogenic?

PSMC3IP p.Arg5Pro (c.14G>C) is classified Uncertain significance in PSMC3IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.3023); Very rare (popmax 0.00333%, amr).

How common is PSMC3IP p.Arg5Pro (c.14G>C) in the general population?

PSMC3IP p.Arg5Pro (c.14G>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PSMC3IP p.Arg5Pro (c.14G>C)?

AlphaMissense predicts likely benign (score 0.3023) — an in-silico prediction, not a clinical call.

PSMC3IP p.Arg5Pro

c.14G>C · VCV3310975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3023 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3023	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -7.99	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 5.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 4,715 bp · p 0.42 · regional, not allelic
Overall
CADD	25.4	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 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00204% 33/1,614,048 alleles · very rare exomes 31/1,461,784 · genomes 2/152,264 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
European (non-Finnish)	0.00246%	40,690
Remaining individualsnot grpmax-eligible	0.0016%	62,482
South Asian	0.0011%	91,092

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.Arg5Pro
Coding: c.14G>C
MANE Select: NM_016556
Type: single nucleotide variant
Location: chr17:42577673 (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

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-arg5pro (accessed [today's date]).

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