Is CSPG4 p.Arg235Trp (c.703C>T) pathogenic?

CSPG4 p.Arg235Trp (c.703C>T) is classified Uncertain significance in CSPG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.0623); Very rare (popmax 0.00223%, eas).

How common is CSPG4 p.Arg235Trp (c.703C>T) in the general population?

CSPG4 p.Arg235Trp (c.703C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CSPG4 p.Arg235Trp (c.703C>T)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

CSPG4 p.Arg235Trp

c.703C>T · VCV4007642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -8.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -0.81, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 204 bp · p 2e-07 · regional, not allelic
Overall
CADD	22.9	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

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00048% 7/1,459,302 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
Remaining individualsnot grpmax-eligible	0.0016%	62,368
South Asian	0.0011%	91,026
European (non-Finnish)	0.000339%	294,897

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.Arg235Trp
Coding: c.703C>T
MANE Select: NM_001897
Type: single nucleotide variant
Location: chr15:75690362 (GRCh38)
Gene constraint: LOEUF 0.693 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.35 · 3 PDB
Residue 235: the 'globular or compact configuration stabilized by disulfide bonds' region; the 'neurite growth inhibition' region; the laminin g-like 2 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-arg235trp (accessed [today's date]).

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