Is DPY19L2 p.Ala487Val (c.1460C>T) pathogenic?

DPY19L2 p.Ala487Val (c.1460C>T) is classified Uncertain significance in DPY19L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: likely benign (0.1128); Very rare (popmax 0.00247%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPY19L2 p.Ala487Val (c.1460C>T)?

DPY19L2 p.Ala487Val (c.1460C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPY19L2 p.Ala487Val (c.1460C>T) in the general population?

DPY19L2 p.Ala487Val (c.1460C>T) is very rare (popmax 0.00247%, nfe) (gnomAD).

What do computational predictors say about DPY19L2 p.Ala487Val (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

DPY19L2 p.Ala487Val

c.1460C>T · rs746978273 · VCV2399143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00247%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.22	GERP -0.35, phastCons 0.086
Regional constraint	o/e 0.66	unconstrained · MANE · 57 kb · p 5.8e-13 · regional, not allelic
Overall
CADD	21.1	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 0.00247% European (non-Finnish) · 29/1,174,098 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0015%

Overall 0.00193% 31/1,603,140 alleles · very rare exomes 27/1,451,260 · genomes 4/151,880 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00247%	40,486
Admixed American	0.00169%	59,070
African / African-American	0.00135%	74,320

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: DPY19L2
Protein: p.Ala487Val
Coding: c.1460C>T
MANE Select: NM_173812
dbSNP: rs746978273
Type: single nucleotide variant
Location: chr12:63597810 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.61

Full DPY19L2 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

DPY19L2 p.Arg23Cys Uncertain significance ★★ ⚠ same condition
DPY19L2 p.Ala432Thr Uncertain significance ★ ⚠ same condition
DPY19L2 p.Ala739Thr Uncertain significance ★ ⚠ same condition
DPY19L2 p.Ala90Val Uncertain significance ★ ⚠ same condition
DPY19L2 p.Arg132His Uncertain significance ★ ⚠ same condition
DPY19L2 p.Arg190Cys Uncertain significance ★ same condition
DPY19L2 p.Arg290Pro Uncertain significance ★ ⚠ same condition
DPY19L2 p.Arg2Thr 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/dpy19l2-p-ala487val (accessed [today's date]).

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