Is DLL1 p.Lys172Arg (c.515A>G) pathogenic?

DLL1 p.Lys172Arg (c.515A>G) is classified Conflicting classifications of pathogenicity in DLL1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-01). AlphaMissense: likely benign (0.0885); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures.

How common is DLL1 p.Lys172Arg (c.515A>G) in the general population?

DLL1 p.Lys172Arg (c.515A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLL1 p.Lys172Arg (c.515A>G)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

DLL1 p.Lys172Arg

Q: What condition is associated with DLL1 p.Lys172Arg (c.515A>G)?

DLL1 p.Lys172Arg (c.515A>G) is associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (ClinVar).

c.515A>G · rs2483358297 · VCV1878299

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -3.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.92	donor gain · deltas
Pangolin	Δ0.54	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.4	GERP -1.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 4,873 bp · p 2e-13 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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: DLL1
Protein: p.Lys172Arg
Coding: c.515A>G
MANE Select: NM_005618
dbSNP: rs2483358297
Type: single nucleotide variant
Location: chr6:170288394 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 172: a UniProt-annotated variant site (in nedbas); a β-strand

Full DLL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL1 p.Arg509Ter Pathogenic ★★ same condition
DLL1 c.413-3T>G Uncertain significance ★★ same condition
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg176Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg392Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg430His 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/dll1-p-lys172arg (accessed [today's date]).

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