Is CSPG4 p.Arg167Ser (c.501G>T) pathogenic?

CSPG4 p.Arg167Ser (c.501G>T) is classified Uncertain significance in CSPG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.8964); Very rare (popmax 0.00837%, amr).

How common is CSPG4 p.Arg167Ser (c.501G>T) in the general population?

CSPG4 p.Arg167Ser (c.501G>T) is very rare (popmax 0.00837%, amr) (gnomAD).

What do computational predictors say about CSPG4 p.Arg167Ser (c.501G>T)?

AlphaMissense predicts likely pathogenic (score 0.8964) — an in-silico prediction, not a clinical call.

CSPG4 p.Arg167Ser

c.501G>T · VCV4235201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00837%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8964	likely pathogenic · top 5% in CSPG4
REVEL	0.609	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3
Regional constraint	o/e 1.00	unconstrained · MANE · 314 bp · p 0.98 · regional, not allelic
Overall
CADD	13.69	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 0.00837% Admixed American · 5/59,768 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.0018% 29/1,608,492 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00956%	10,463
Admixed Americangrpmax	0.00837%	11,954
African / African-American	0.00402%	24,899
East Asian	0.00223%	44,852
Remaining individualsnot grpmax-eligible	0.00161%	62,154
European (non-Finnish)	0.0011%	90,662

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg167Ser
Coding: c.501G>T
MANE Select: NM_001897
Type: single nucleotide variant
Location: chr15:75690564 (GRCh38)
Gene constraint: LOEUF 0.693 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.35 · 3 PDB
Residue 167: 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-arg167ser (accessed [today's date]).

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