Is DPY19L1 p.Arg22Pro (c.65G>C) pathogenic?

DPY19L1 p.Arg22Pro (c.65G>C) is classified Uncertain significance in DPY19L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0887); Very rare (popmax 0.000101%, nfe).

How common is DPY19L1 p.Arg22Pro (c.65G>C) in the general population?

DPY19L1 p.Arg22Pro (c.65G>C) is very rare (popmax 0.000101%, nfe) (gnomAD).

What do computational predictors say about DPY19L1 p.Arg22Pro (c.65G>C)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

DPY19L1 p.Arg22Pro

c.65G>C · VCV4244607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000101%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.97	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 -0.92	GERP -0.2
Overall
CADD	1.928	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 0.000101% European (non-Finnish) · 1/985,392 alleles

Overall 9.27e-05% 1/1,078,982 alleles · very rare

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: DPY19L1
Protein: p.Arg22Pro
Coding: c.65G>C
MANE Select: NM_001366673 · reported on NM_015283
Type: single nucleotide variant
Location: chr7:35037832 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 88.51
Residue 22: the 'disordered' region

Full DPY19L1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPY19L1 p.Ala132Val Uncertain significance ★ ⚠ same type
DPY19L1 p.Ala340Val Uncertain significance ★ ⚠ same type
DPY19L1 p.Ala386Val Uncertain significance ★ ⚠ same type
DPY19L1 p.Ala397Ser Uncertain significance ★ ⚠ same type
DPY19L1 p.Arg119His Uncertain significance ★ ⚠ same type
DPY19L1 p.Arg14Cys Uncertain significance ★ ⚠ same type
DPY19L1 p.Arg177Ser Uncertain significance ★ ⚠ same type
DPY19L1 p.Arg258Gln 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/dpy19l1-p-arg22pro (accessed [today's date]).

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