Is CYP24A1 p.Ala487Val (c.1460C>T) pathogenic?

CYP24A1 p.Ala487Val (c.1460C>T) is classified Likely benign in CYP24A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-13). AlphaMissense: likely benign (0.1862); Ultra-rare (popmax 0.049%, eas).

How common is CYP24A1 p.Ala487Val (c.1460C>T) in the general population?

CYP24A1 p.Ala487Val (c.1460C>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about CYP24A1 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.1862) — an in-silico prediction, not a clinical call.

CYP24A1 p.Ala487Val

c.1460C>T · rs531438091 · VCV1622534

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1862	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -7.97	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 16 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	26.9	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 0.049% East Asian · 22/44,882 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00155% 25/1,611,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
Remaining individualsnot grpmax-eligible	0.0032%	31,206
European (non-Finnish)	8.49e-05%	1,178,024

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: CYP24A1
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_000782
dbSNP: rs531438091
Type: single nucleotide variant
Location: chr20:54157264 (GRCh38)
Gene constraint: LOEUF 1.507 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.03

Full CYP24A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP24A1 p.Arg159Gln Pathogenic/Likely pathogenic ★★ same type
CYP24A1 p.Arg159Trp Pathogenic/Likely pathogenic ★★ same type
CYP24A1 p.Arg223Ter Pathogenic ★★ same type
CYP24A1 p.Arg396Gln Pathogenic/Likely pathogenic ★★ same type
CYP24A1 p.Arg396Trp Pathogenic/Likely pathogenic ★★ same type
CYP24A1 p.Arg466Ter Pathogenic ★★ same type
CYP24A1 p.Gln347Ter Pathogenic/Likely pathogenic ★★ same type
CYP24A1 p.Gln442Ter Pathogenic/Likely pathogenic ★★ same type

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/cyp24a1-p-ala487val (accessed [today's date]).

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