Is PHLPP2 p.Pro882Ala (c.2644C>G) pathogenic?

PHLPP2 p.Pro882Ala (c.2644C>G) is classified Uncertain significance in PHLPP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0802); Very rare (popmax 0.00195%, nfe).

How common is PHLPP2 p.Pro882Ala (c.2644C>G) in the general population?

PHLPP2 p.Pro882Ala (c.2644C>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about PHLPP2 p.Pro882Ala (c.2644C>G)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

PHLPP2 p.Pro882Ala

c.2644C>G · rs569703138 · VCV2246346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -9.29	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 66 kb · p 0.034 · regional, not allelic
Overall
CADD	23.6	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 0.00195% European (non-Finnish) · 23/1,180,040 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00143% 23/1,613,918 alleles · very rare

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: PHLPP2
Protein: p.Pro882Ala
Coding: c.2644C>G
MANE Select: NM_015020
dbSNP: rs569703138
Type: single nucleotide variant
Location: chr16:71652963 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.11
Residue 882: the ppm-type phosphatase domain

Full PHLPP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHLPP2 p.Asp453Gly Uncertain significance ★★ ⚠ same type
PHLPP2 p.Ile204Val Likely benign ★★ same type
PHLPP2 p.Ser1139Cys Likely benign ★★ same type
PHLPP2 p.Ala1008Thr Uncertain significance ★ ⚠ same type
PHLPP2 p.Ala1008Val Uncertain significance ★ ⚠ same type
PHLPP2 p.Ala1270Ser Uncertain significance ★ ⚠ same type
PHLPP2 p.Ala1322Val Uncertain significance ★ ⚠ same type
PHLPP2 p.Ala223Pro 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/phlpp2-p-pro882ala (accessed [today's date]).

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