Is DPY19L1 p.Gln588Pro (c.1763A>C) pathogenic?

DPY19L1 p.Gln588Pro (c.1763A>C) is classified Uncertain significance in DPY19L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-19). AlphaMissense: likely benign (0.1844); Very rare (popmax 0.00223%, eas).

How common is DPY19L1 p.Gln588Pro (c.1763A>C) in the general population?

DPY19L1 p.Gln588Pro (c.1763A>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DPY19L1 p.Gln588Pro (c.1763A>C)?

AlphaMissense predicts likely benign (score 0.1844) — an in-silico prediction, not a clinical call.

DPY19L1 p.Gln588Pro

c.1763A>C · VCV3273677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1844 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1844	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 106 kb · p 3.2e-20 · regional, not allelic
Overall
CADD	25.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q515P vs ClinVar Q588P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,840 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000744% 12/1,612,600 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,840
Admixed American	0.00167%	59,978
Remaining individualsnot grpmax-eligible	0.0016%	62,380
African / African-American	0.00134%	74,880
South Asian	0.0011%	90,988
European (non-Finnish)	0.000593%	168,554

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.Gln588Pro
Coding: c.1763A>C
MANE Select: NM_001366673
Type: single nucleotide variant
Location: chr7:34940254 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 88.51

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.Arg22Pro 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-gln588pro (accessed [today's date]).

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