Is PMPCA p.Pro54Ser (c.160C>T) pathogenic?

PMPCA p.Pro54Ser (c.160C>T) is classified Uncertain significance in PMPCA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). AlphaMissense: ambiguous (0.4828); Absent from gnomAD v4.1; Associated with autosomal recessive spinocerebellar ataxia 2.

What condition is associated with PMPCA p.Pro54Ser (c.160C>T)?

PMPCA p.Pro54Ser (c.160C>T) is associated with autosomal recessive spinocerebellar ataxia 2 (ClinVar).

How common is PMPCA p.Pro54Ser (c.160C>T) in the general population?

PMPCA p.Pro54Ser (c.160C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PMPCA p.Pro54Ser (c.160C>T)?

AlphaMissense predicts ambiguous (score 0.4828) — an in-silico prediction, not a clinical call.

PMPCA p.Pro54Ser

Q: How is Autosomal recessive cerebelloparenchymal disorder type 3 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.160C>T · rs2538835672 · VCV1802623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive spinocerebellar ataxia 2

Computational evidence

Protein change
AlphaMissense	0.4828	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -9.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -0.021, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 13 kb · p 0.42 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PMPCA
Protein: p.Pro54Ser
Coding: c.160C>T
MANE Select: NM_015160
dbSNP: rs2538835672
Type: single nucleotide variant
Location: chr9:136412085 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.46

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

Disease context

autosomal recessive spinocerebellar ataxia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cerebelloparenchymal disorder type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

INPP5E p.Thr54Ile Uncertain significance ★★ ⚠ same residue
INPP5E p.Thr54Ser Uncertain significance ★ ⚠ same residue
PMPCA p.Gln86His Uncertain significance ★★ ⚠ same condition
PMPCA p.Thr162Met Uncertain significance ★★ ⚠ same condition
PMPCA p.Val367Met Uncertain significance ★★ ⚠ same condition
PMPCA c.1200+33G>A Benign ★★ same condition
PMPCA p.Tyr30= Benign ★★ same condition
PMPCA c.1408+1G>A Pathogenic ★ same condition

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/pmpca-p-pro54ser (accessed [today's date]).

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