Is PPM1B p.Asp381Asn (c.1141G>A) pathogenic?

PPM1B p.Asp381Asn (c.1141G>A) is classified Likely benign in PPM1B (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1041); Rare (popmax 0.395%, nfe).

How common is PPM1B p.Asp381Asn (c.1141G>A) in the general population?

PPM1B p.Asp381Asn (c.1141G>A) is rare (popmax 0.395%, nfe) (gnomAD).

What do computational predictors say about PPM1B p.Asp381Asn (c.1141G>A)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

PPM1B p.Asp381Asn

c.1141G>A · rs139541400 · VCV708633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.395%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -6.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 29 kb · p 2.9e-07 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.395% European (non-Finnish) · 4,664/1,179,634 alleles

Filtering AF 0.386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.382%

Overall 0.33% 5,317/1,613,530 alleles · rare exomes 4,929/1,461,242 · genomes 388/152,288 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.804%	124
European (non-Finnish)grpmax	0.395%	253
Remaining individualsnot grpmax-eligible	0.277%	361
Admixed American	0.132%	759
Finnishnot grpmax-eligible	0.111%	902
African / African-American	0.0907%	1,103
Middle Eastern	0.0495%	2,020
South Asian	0.0231%	4,334

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PPM1B
Protein: p.Asp381Asn
Coding: c.1141G>A
MANE Select: NM_002706
dbSNP: rs139541400
Type: single nucleotide variant
Location: chr2:44230419 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 85.52 · 1 PDB

Full PPM1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPM1B p.Gln161Glu Uncertain significance ★★ ⚠ same type
PPM1B c.1134+10A>G Benign ★★ same type
PPM1B p.Ala201Thr Uncertain significance ★ ⚠ same type
PPM1B p.Ala298Val Uncertain significance ★ ⚠ same type
PPM1B p.Ala305Val Uncertain significance ★ ⚠ same type
PPM1B p.Ala344Thr Uncertain significance ★ ⚠ same type
PPM1B p.Ala395Thr Uncertain significance ★ ⚠ same type
PPM1B p.Ala433Pro 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/ppm1b-p-asp381asn (accessed [today's date]).

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