Is PPIP5K2 p.Ser68Phe (c.203C>T) pathogenic?

PPIP5K2 p.Ser68Phe (c.203C>T) is classified Uncertain significance in PPIP5K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2455); Absent from gnomAD v4.1.

How common is PPIP5K2 p.Ser68Phe (c.203C>T) in the general population?

PPIP5K2 p.Ser68Phe (c.203C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIP5K2 p.Ser68Phe (c.203C>T)?

AlphaMissense predicts likely benign (score 0.2455) — an in-silico prediction, not a clinical call.

PPIP5K2 p.Ser68Phe

c.203C>T · VCV4570879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2455	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6	GERP 0.97, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 0.00081 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPIP5K2
Protein: p.Ser68Phe
Coding: c.203C>T
MANE Select: NM_001276277
Type: single nucleotide variant
Location: chr5:103133541 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.73 · 21 PDB

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-ser68phe (accessed [today's date]).

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