Is VLDLR p.Ser701= (c.2103A>C) pathogenic?

VLDLR p.Ser701= (c.2103A>C) is classified Uncertain significance in VLDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Absent from gnomAD v4.1; Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1.

What condition is associated with VLDLR p.Ser701= (c.2103A>C)?

VLDLR p.Ser701= (c.2103A>C) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (ClinVar).

How common is VLDLR p.Ser701= (c.2103A>C) in the general population?

VLDLR p.Ser701= (c.2103A>C) is absent from gnomAD v4.1 (gnomAD).

How is Dysequilibrium syndrome inherited?

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

VLDLR p.Ser701=

c.2103A>C · rs886063811 · VCV366373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	donor loss · deltas
Pangolin	Δ0.56	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Overall
CADD	19.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VLDLR
Protein: p.Ser701=
Coding: c.2103A>C
MANE Select: NM_003383
dbSNP: rs886063811
Type: single nucleotide variant
Location: chr9:2648809 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 27 PDB

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-ser701 (accessed [today's date]).

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