Is PMP2 p.Ser44Arg (c.130A>C) pathogenic?

PMP2 p.Ser44Arg (c.130A>C) is classified Likely benign in PMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). AlphaMissense: ambiguous (0.3723); Very rare (popmax 0.000593%, nfe).

How common is PMP2 p.Ser44Arg (c.130A>C) in the general population?

PMP2 p.Ser44Arg (c.130A>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about PMP2 p.Ser44Arg (c.130A>C)?

AlphaMissense predicts ambiguous (score 0.3723) — an in-silico prediction, not a clinical call.

PMP2 p.Ser44Arg

c.130A>C · rs367715450 · VCV1593682

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3723	ambiguous
REVEL	0.134	moderately benign-leaning
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,985 bp · p 0.81 · regional, not allelic
Overall
CADD	23.4	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 0.000593% European (non-Finnish) · 7/1,179,908 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00372% 60/1,613,916 alleles · very rare exomes 50/1,461,662 · genomes 10/152,254 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.166%	604
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)grpmax	0.000593%	168,558

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: PMP2
Protein: p.Ser44Arg
Coding: c.130A>C
MANE Select: NM_002677
dbSNP: rs367715450
Type: single nucleotide variant
Location: chr8:81444933 (GRCh38)
Gene constraint: LOEUF 1.511 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.49 · 30 PDB
Residue 44: a β-strand

Full PMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PMP2 p.Ile43Asn Pathogenic/Likely pathogenic ★★ same type
PMP2 p.Ile52Thr Pathogenic/Likely pathogenic ★★ same type
PMP2 p.Ala116= Uncertain significance ★★ same type
PMP2 p.Arg53Gln Uncertain significance ★★ ⚠ same type
PMP2 p.Asn60Thr Uncertain significance ★★ ⚠ same type
PMP2 p.Asp19Asn Uncertain significance ★★ ⚠ same type
PMP2 p.Asp48Asn Uncertain significance ★★ ⚠ same type
PMP2 p.Glu130Lys 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/pmp2-p-ser44arg (accessed [today's date]).

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