Is DPY19L1 p.Ile111Val (c.331A>G) pathogenic?

DPY19L1 p.Ile111Val (c.331A>G) is classified Uncertain significance in DPY19L1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.1468); Very rare (popmax 0.000255%, nfe).

How common is DPY19L1 p.Ile111Val (c.331A>G) in the general population?

DPY19L1 p.Ile111Val (c.331A>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about DPY19L1 p.Ile111Val (c.331A>G)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

DPY19L1 p.Ile111Val

c.331A>G · VCV4662031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -3.89	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 1.5	GERP -0.96, phastCons 0.99
Regional constraint	o/e 0.67	unconstrained · MANE · 106 kb · p 3.2e-20 · regional, not allelic
Overall
CADD	22.1	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 I38V vs ClinVar I111V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,174,242 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00131% 21/1,602,602 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0613%	1,631
European (non-Finnish)grpmax	0.000255%	391,414

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile111Val
Coding: c.331A>G
MANE Select: NM_001366673
Type: single nucleotide variant
Location: chr7:35017962 (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-ile111val (accessed [today's date]).

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