Is CSPG4 p.Ala280Val (c.839C>T) pathogenic?

CSPG4 p.Ala280Val (c.839C>T) is classified Uncertain significance in CSPG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.17); Ultra-rare (popmax 0.0217%, amr).

How common is CSPG4 p.Ala280Val (c.839C>T) in the general population?

CSPG4 p.Ala280Val (c.839C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about CSPG4 p.Ala280Val (c.839C>T)?

AlphaMissense predicts likely benign (score 0.17) — an in-silico prediction, not a clinical call.

CSPG4 p.Ala280Val

c.839C>T · VCV3836912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.17 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.17	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -0.91, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 15 kb · p 3.1e-21 · regional, not allelic
Overall
CADD	22.4	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 0.0217% Admixed American · 13/60,012 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000958% 14/1,461,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
East Asian	0.00223%	44,886

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.Ala280Val
Coding: c.839C>T
MANE Select: NM_001897
Type: single nucleotide variant
Location: chr15:75690226 (GRCh38)
Gene constraint: LOEUF 0.693 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.35 · 3 PDB
Residue 280: 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-ala280val (accessed [today's date]).

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