Is DPY19L3 p.Pro218Arg (c.653C>G) pathogenic?

DPY19L3 p.Pro218Arg (c.653C>G) is classified Uncertain significance in DPY19L3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1.

How common is DPY19L3 p.Pro218Arg (c.653C>G) in the general population?

DPY19L3 p.Pro218Arg (c.653C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPY19L3 p.Pro218Arg (c.653C>G)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

DPY19L3 p.Pro218Arg

c.653C>G · rs1411457041 · VCV2335151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 2% in DPY19L3
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -15.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 74 kb · p 3e-07 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPY19L3
Protein: p.Pro218Arg
Coding: c.653C>G
MANE Select: NM_001172774
dbSNP: rs1411457041
Type: single nucleotide variant
Location: chr19:32439168 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.89

Full DPY19L3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPY19L3 p.Ala173Gly Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala192Thr Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala464Thr Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala495Thr Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala54Ser Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala576Val Uncertain significance ★ ⚠ same type
DPY19L3 p.Ala583Ser Uncertain significance ★ same type
DPY19L3 p.Arg232Thr Uncertain significance ★ 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/dpy19l3-p-pro218arg (accessed [today's date]).

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