Is PMP2 p.Ser91Ala (c.271T>G) pathogenic?

PMP2 p.Ser91Ala (c.271T>G) is classified Likely benign in PMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-17). AlphaMissense: likely benign (0.0846); Ultra-rare (popmax 0.0923%, sas).

How common is PMP2 p.Ser91Ala (c.271T>G) in the general population?

PMP2 p.Ser91Ala (c.271T>G) is ultra-rare (popmax 0.0923%, sas) (gnomAD).

What do computational predictors say about PMP2 p.Ser91Ala (c.271T>G)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

PMP2 p.Ser91Ala

c.271T>G · rs768313060 · VCV2416504

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0923%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -4.76	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
Conservation	phyloP -0.28	GERP -1.8
Regional constraint	o/e 0.98	unconstrained · MANE · 3,985 bp · p 0.81 · regional, not allelic
Overall
CADD	5.157	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 0.0923% South Asian · 84/91,052 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00539% 87/1,613,742 alleles · ultra-rare exomes 86/1,461,620 · genomes 1/152,122 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0923%	1,084
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	59,996

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.Ser91Ala
Coding: c.271T>G
MANE Select: NM_002677
dbSNP: rs768313060
Type: single nucleotide variant
Location: chr8:81444577 (GRCh38)
Gene constraint: LOEUF 1.511 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.49 · 30 PDB
Residue 91: 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-ser91ala (accessed [today's date]).

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