Is PSMC3IP p.Val212Phe (c.634G>T) pathogenic?

PSMC3IP p.Val212Phe (c.634G>T) is classified Uncertain significance in PSMC3IP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-27). AlphaMissense: likely benign (0.24); Very rare (popmax 0.00549%, sas).

How common is PSMC3IP p.Val212Phe (c.634G>T) in the general population?

PSMC3IP p.Val212Phe (c.634G>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about PSMC3IP p.Val212Phe (c.634G>T)?

AlphaMissense predicts likely benign (score 0.24) — an in-silico prediction, not a clinical call.

PSMC3IP p.Val212Phe

c.634G>T · rs149230650 · VCV2606627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.24 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.24	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.8	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 4,715 bp · p 0.42 · regional, not allelic
Overall
CADD	24.2	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 0.00549% South Asian · 5/91,084 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000434% 7/1,614,216 alleles · very rare exomes 7/1,461,872 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	8.47e-05%	1,180,044

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.Val212Phe
Coding: c.634G>T
MANE Select: NM_016556
dbSNP: rs149230650
Type: single nucleotide variant
Location: chr17:42572988 (GRCh38)

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

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-val212phe (accessed [today's date]).

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