Is CSPG4 p.Arg82Cys (c.244C>T) pathogenic?

CSPG4 p.Arg82Cys (c.244C>T) is classified Uncertain significance in CSPG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0818); Rare (popmax 0.327%, afr).

How common is CSPG4 p.Arg82Cys (c.244C>T) in the general population?

CSPG4 p.Arg82Cys (c.244C>T) is rare (popmax 0.327%, afr) (gnomAD).

What do computational predictors say about CSPG4 p.Arg82Cys (c.244C>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

CSPG4 p.Arg82Cys

c.244C>T · VCV4235241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.327%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.2, phastCons 0.01
Regional constraint	o/e 0.50	unconstrained · MANE · 2,402 bp · p 0.0001 · regional, not allelic
Overall
CADD	20.4	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 0.327% African / African-American · 239/73,010 alleles

Filtering AF 0.293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.0193% 287/1,490,582 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.327%	305
Middle Eastern	0.0237%	4,228
Remaining individualsnot grpmax-eligible	0.0121%	8,299
Admixed American	0.00967%	10,343
East Asian	0.00727%	13,761
European (non-Finnish)	0.00284%	35,164
South Asian	0.0012%	83,084

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: CSPG4
Protein: p.Arg82Cys
Coding: c.244C>T
MANE Select: NM_001897
Type: single nucleotide variant
Location: chr15:75693078 (GRCh38)
Gene constraint: LOEUF 0.693 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.35 · 3 PDB
Residue 82: the 'globular or compact configuration stabilized by disulfide bonds' region; the 'neurite growth inhibition' region; the laminin g-like 1 domain

Full CSPG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSPG4 p.Arg2169Trp Uncertain significance ★★ ⚠ same type
CSPG4 p.Arg1557His Likely benign ★★ same type
CSPG4 p.Ser1882= Likely benign ★★ same type
CSPG4 p.Thr305Met Benign ★★ ⚠ same type
CSPG4 p.Ala1116Val Uncertain significance ★ ⚠ same type
CSPG4 p.Ala1186Val Uncertain significance ★ ⚠ same type
CSPG4 p.Ala1212Val Uncertain significance ★ ⚠ same type
CSPG4 p.Ala121Thr 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/cspg4-p-arg82cys (accessed [today's date]).

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