Is VDR p.Arg18Gln (c.53G>A) pathogenic?

VDR p.Arg18Gln (c.53G>A) is classified Uncertain significance in VDR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.2302); Ultra-rare (popmax 0.0117%, amr); Associated with VDR-related disorder.

What condition is associated with VDR p.Arg18Gln (c.53G>A)?

VDR p.Arg18Gln (c.53G>A) is associated with VDR-related disorder (ClinVar).

How common is VDR p.Arg18Gln (c.53G>A) in the general population?

VDR p.Arg18Gln (c.53G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about VDR p.Arg18Gln (c.53G>A)?

AlphaMissense predicts likely benign (score 0.2302) — an in-silico prediction, not a clinical call.

VDR p.Arg18Gln

c.53G>A · rs115085431 · VCV3032901

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2302 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

VDR-related disorder

Computational evidence

Protein change
AlphaMissense	0.2302	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.68, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.98 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,018 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00217% 35/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,574
African / African-American	0.00933%	10,719
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,510
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)	0.00144%	69,414
South Asian	0.0011%	91,084

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.Arg18Gln
Coding: c.53G>A
MANE Select: NM_000376
dbSNP: rs115085431
Type: single nucleotide variant
Location: chr12:47879061 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 52 PDB

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

Disease context

VDR-related disorder

Similar variants

VDR p.Arg18Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
VDR p.Arg18= Likely benign ★ same residue
VDR p.Arg30Ter Pathogenic ★★ same condition
VDR p.Tyr295Ter Pathogenic ★★ same condition
VDR p.Val346Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
VDR p.Val261Ile Uncertain significance ★★ ⚠ same condition
VDR c.584-2A>G Likely pathogenic ★ same condition
VDR p.Asp17His 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-arg18gln (accessed [today's date]).

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