Is DLL4 p.Gly262Ser (c.784G>A) pathogenic?

DLL4 p.Gly262Ser (c.784G>A) is classified Likely pathogenic in DLL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). AlphaMissense: likely pathogenic (0.8262); Absent from gnomAD v4.1; Associated with Adams-Oliver syndrome 6.

What condition is associated with DLL4 p.Gly262Ser (c.784G>A)?

DLL4 p.Gly262Ser (c.784G>A) is associated with Adams-Oliver syndrome 6 (ClinVar).

How common is DLL4 p.Gly262Ser (c.784G>A) in the general population?

DLL4 p.Gly262Ser (c.784G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLL4 p.Gly262Ser (c.784G>A)?

AlphaMissense predicts likely pathogenic (score 0.8262) — an in-silico prediction, not a clinical call.

DLL4 p.Gly262Ser

c.784G>A · rs2140369593 · VCV1320129

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8262 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 6

Computational evidence

Protein change
AlphaMissense	0.8262	likely pathogenic ✓ concordant with ClinVar
REVEL	0.705	pathogenic-leaning
SaProt	LLR -12.21	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 2,750 bp · p 8.1e-14 · regional, not allelic
Overall
CADD	32.0	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: DLL4
Protein: p.Gly262Ser
Coding: c.784G>A
MANE Select: NM_019074
dbSNP: rs2140369593
Type: single nucleotide variant
Location: chr15:40932381 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.89 · 1 PDB
Residue 262: a disulfide bond; the egf-like 2 domain; a β-strand

Full DLL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Adams-Oliver syndrome 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL4 p.Cys390Tyr Pathogenic/Likely pathogenic ★★ same condition
DLL4 p.Cys466Arg Likely pathogenic ★★ same condition
DLL4 p.Gln584Ter Pathogenic/Likely pathogenic ★★ same condition
DLL4 c.1240+5G>A Likely pathogenic ★ same condition
DLL4 p.Ala121Pro Pathogenic ★ same condition
DLL4 p.Arg186Cys Pathogenic ★ same condition
DLL4 p.Arg558Ter Pathogenic ★ same condition
DLL4 p.Cys390Arg Pathogenic ★ 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/dll4-p-gly262ser (accessed [today's date]).

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