Is VDR p.Pro170Ser (c.508C>T) pathogenic?

VDR p.Pro170Ser (c.508C>T) is classified Likely benign in VDR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0709); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with VDR p.Pro170Ser (c.508C>T)?

VDR p.Pro170Ser (c.508C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VDR p.Pro170Ser (c.508C>T) in the general population?

VDR p.Pro170Ser (c.508C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about VDR p.Pro170Ser (c.508C>T)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

VDR p.Pro170Ser

c.508C>T · VCV4198629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3
Regional constraint	o/e 1.14	unconstrained · MANE · 1,493 bp · p 0.24 · regional, not allelic
Overall
CADD	3.352	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 6.84e-05%

Overall 6.84e-05% 1/1,461,874 alleles · very rare

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: VDR
Protein: p.Pro170Ser
Coding: c.508C>T
MANE Select: NM_000376
Type: single nucleotide variant
Location: chr12:47857204 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB
Residue 170: the nr lbd domain; a UniProt-annotated variant site (in vddr2a; loss of calcitriol receptor activity; loss of affinity for calcitriol; no effect on ligand-independent localization to the nucleus); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VDR p.Pro170His Uncertain significance ★★ ⚠ same residue
VDR c.147-5G>A Uncertain significance ★★ same condition
VDR p.Arg130His Uncertain significance ★★ ⚠ same condition
VDR p.Arg368Leu Uncertain significance ★★ ⚠ same condition
VDR p.Asp181Asn Uncertain significance ★★ ⚠ same condition
VDR p.Asp181Gly Uncertain significance ★★ ⚠ same condition
VDR p.Asp253Glu Uncertain significance ★★ ⚠ same condition
VDR p.Asp292His 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/vdr-p-pro170ser (accessed [today's date]).

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