Is VDR p.Ala6Val (c.17C>T) pathogenic?

VDR p.Ala6Val (c.17C>T) is classified Uncertain significance in VDR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.1234); Ultra-rare (popmax 0.0132%, sas); Associated with Inborn genetic diseases.

What condition is associated with VDR p.Ala6Val (c.17C>T)?

VDR p.Ala6Val (c.17C>T) is associated with Inborn genetic diseases (ClinVar).

How common is VDR p.Ala6Val (c.17C>T) in the general population?

VDR p.Ala6Val (c.17C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about VDR p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

VDR p.Ala6Val

c.17C>T · rs765563014 · VCV2261491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -7.25	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 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.98 · regional, not allelic
Overall
CADD	18.96	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 0.0132% South Asian · 12/91,074 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000889% 13/1,461,688 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,589
African / African-American	0.00133%	75,024

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.Ala6Val
Coding: c.17C>T
MANE Select: NM_000376
dbSNP: rs765563014
Type: single nucleotide variant
Location: chr12:47879097 (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

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

Similar variants

VDR p.Ala6= Likely benign ★ 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-ala6val (accessed [today's date]).

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