Is PPIP5K2 p.Phe925Ser (c.2774T>C) pathogenic?

PPIP5K2 p.Phe925Ser (c.2774T>C) is classified Uncertain significance in PPIP5K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely benign (0.0674); No allele count reported in gnomAD v4.1 (AN 1,543,756).

How common is PPIP5K2 p.Phe925Ser (c.2774T>C) in the general population?

PPIP5K2 p.Phe925Ser (c.2774T>C) is no allele count reported in gnomAD v4.1 (AN 1,543,756) (gnomAD).

What do computational predictors say about PPIP5K2 p.Phe925Ser (c.2774T>C)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

PPIP5K2 p.Phe925Ser

c.2774T>C · VCV4142507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,543,756)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -3.68	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 0.38	GERP -2.8, phastCons 0.76
Regional constraint	o/e 0.91	unconstrained · MANE · 7,294 bp · p 0.18 · regional, not allelic
Overall
CADD	11.84	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

No allele count reported in gnomAD v4.1 (AN 1,543,756). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPIP5K2
Protein: p.Phe925Ser
Coding: c.2774T>C
MANE Select: NM_001276277
Type: single nucleotide variant
Location: chr5:103180040 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.73 · 21 PDB
Residue 925: the 'disordered' region

Full PPIP5K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPIP5K2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
PPIP5K2 p.Ala1168Thr Uncertain significance ★ ⚠ same type
PPIP5K2 p.Ala1207Val Uncertain significance ★ ⚠ same type
PPIP5K2 p.Ala28Val Uncertain significance ★ ⚠ same type
PPIP5K2 p.Ala300Gly Uncertain significance ★ ⚠ same type
PPIP5K2 p.Arg1001His Uncertain significance ★ ⚠ same type
PPIP5K2 p.Arg1002Gln Uncertain significance ★ ⚠ same type
PPIP5K2 p.Arg1005Lys Uncertain significance ★ ⚠ 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/ppip5k2-p-phe925ser (accessed [today's date]).

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