Is VLDLR p.Asp213= (c.639C>T) pathogenic?

VLDLR p.Asp213= (c.639C>T) is classified Conflicting classifications of pathogenicity in VLDLR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-16). Ultra-rare (popmax 0.0209%, sas); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1.

What condition is associated with VLDLR p.Asp213= (c.639C>T)?

VLDLR p.Asp213= (c.639C>T) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (ClinVar).

How common is VLDLR p.Asp213= (c.639C>T) in the general population?

VLDLR p.Asp213= (c.639C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

How is Dysequilibrium syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

VLDLR p.Asp213=

c.639C>T · rs779155452 · VCV912550

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -4
Overall
CADD	0.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/91,086 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00774% 125/1,613,988 alleles · ultra-rare exomes 115/1,461,872 · genomes 10/152,116 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00763%	13,111
Admixed American	0.00667%	14,997
Finnishnot grpmax-eligible	0.00625%	16,007
African / African-American	0.00267%	37,446
East Asian	0.00223%	44,878

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: VLDLR
Protein: p.Asp213=
Coding: c.639C>T
MANE Select: NM_003383
dbSNP: rs779155452
Type: single nucleotide variant
Location: chr9:2643350 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 27 PDB
Residue 213: a β-strand; the ldl-receptor class a 5 domain

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

Disease context

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysequilibrium syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

VLDLR c.2252-2A>C Likely pathogenic ★★ same condition
VLDLR c.449-2A>T Likely pathogenic ★★ same condition
VLDLR c.83-1G>A Pathogenic/Likely pathogenic ★★ same condition
VLDLR p.Arg279Ter Pathogenic ★★ same condition
VLDLR p.Arg301Ter Pathogenic ★★ same condition
VLDLR c.-154C>G Uncertain significance ★★ same condition
VLDLR c.-392C>T Uncertain significance ★★ same condition
VLDLR c.*48C>T Uncertain significance ★★ same condition

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/vldlr-p-asp213 (accessed [today's date]).

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