Is PHLPP1 p.Pro282Ser (c.844C>T) pathogenic?

PHLPP1 p.Pro282Ser (c.844C>T) is classified Uncertain significance in PHLPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.000313%, nfe).

How common is PHLPP1 p.Pro282Ser (c.844C>T) in the general population?

PHLPP1 p.Pro282Ser (c.844C>T) is very rare (popmax 0.000313%, nfe) (gnomAD).

What do computational predictors say about PHLPP1 p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

PHLPP1 p.Pro282Ser

c.844C>T · rs1484749751 · VCV3212356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000313%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Regional constraint	o/e 1.13	unconstrained · MANE · 1,354 bp · p 0.001 · regional, not allelic
Overall
CADD	3.914	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 0.000313% European (non-Finnish) · 3/959,068 alleles

Filtering AF 8.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.3e-05%

Overall 0.000253% 3/1,185,270 alleles · very rare exomes 2/1,035,238 · genomes 1/150,032 · 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: PHLPP1
Protein: p.Pro282Ser
Coding: c.844C>T
MANE Select: NM_194449
dbSNP: rs1484749751
Type: single nucleotide variant
Location: chr18:62716527 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 66.08
Residue 282: the 'disordered' region

Full PHLPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHLPP1 p.Ala876Val Uncertain significance ★★ ⚠ same type
PHLPP1 p.His197= Benign ★★ same type
PHLPP1 p.Phe291Val Benign ★★ same type
PHLPP1 p.Pro1690= Benign ★★ same type
PHLPP1 p.Ala1004Val Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala107Thr Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala112Val Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala1167Thr 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/phlpp1-p-pro282ser (accessed [today's date]).

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