Is VLDLR p.Pro156= (c.468C>T) pathogenic?

VLDLR p.Pro156= (c.468C>T) is classified Benign/Likely benign in VLDLR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.89%, eas); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1.

What condition is associated with VLDLR p.Pro156= (c.468C>T)?

VLDLR p.Pro156= (c.468C>T) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (ClinVar).

How common is VLDLR p.Pro156= (c.468C>T) in the general population?

VLDLR p.Pro156= (c.468C>T) is low-frequency (popmax 3.89%, eas) (gnomAD).

How is Dysequilibrium syndrome inherited?

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

VLDLR p.Pro156=

c.468C>T · rs2242105 · VCV130712

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.89%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.4	GERP -4
Overall
CADD	1.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.89% East Asian · 1,746/44,886 alleles

Filtering AF 3.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.117% 1,887/1,612,592 alleles · low-frequency exomes 1,749/1,460,314 · genomes 138/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.89%	26
Remaining individualsnot grpmax-eligible	0.0912%	1,097
South Asian	0.0285%	3,503
Admixed American	0.01%	10,004
European (non-Finnish)	0.00415%	24,082
African / African-American	0.00267%	37,505
Finnishnot grpmax-eligible	0.0016%	62,480

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.Pro156=
Coding: c.468C>T
MANE Select: NM_003383
dbSNP: rs2242105
Type: single nucleotide variant
Location: chr9:2643179 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 27 PDB
Residue 156: the ldl-receptor class a 4 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 p.Pro156His Uncertain significance ★ ⚠ same residue
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

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-pro156 (accessed [today's date]).

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