Is PMPCA p.Lys68Arg (c.203A>G) pathogenic?

PMPCA p.Lys68Arg (c.203A>G) is classified Uncertain significance in PMPCA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-06). AlphaMissense: likely benign (0.0678); Absent from gnomAD v4.1.

How common is PMPCA p.Lys68Arg (c.203A>G) in the general population?

PMPCA p.Lys68Arg (c.203A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PMPCA p.Lys68Arg (c.203A>G)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

PMPCA p.Lys68Arg

c.203A>G · rs1835143289 · VCV2699371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.71	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 -0.037	GERP -2.6, phastCons 0.011
Regional constraint	o/e 1.03	unconstrained · MANE · 13 kb · p 0.42 · regional, not allelic
Overall
CADD	15.18	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

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.Lys68Arg
Coding: c.203A>G
MANE Select: NM_015160
dbSNP: rs1835143289
Type: single nucleotide variant
Location: chr9:136412128 (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

Similar variants

INPP5E c.937-2A>G Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg378Cys Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg435Gln Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg435Trp Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg557His Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg563His Likely pathogenic ★★ ⚠ same type
INPP5E p.Arg585Cys Pathogenic/Likely pathogenic ★★ same type
INPP5E p.Arg621Gln Pathogenic/Likely pathogenic ★★ ⚠ 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/pmpca-p-lys68arg (accessed [today's date]).

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