Is DLL1 p.Arg207Ser (c.619C>A) pathogenic?

DLL1 p.Arg207Ser (c.619C>A) is classified Uncertain significance in DLL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). AlphaMissense: likely benign (0.2239); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with DLL1 p.Arg207Ser (c.619C>A)?

DLL1 p.Arg207Ser (c.619C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DLL1 p.Arg207Ser (c.619C>A) in the general population?

DLL1 p.Arg207Ser (c.619C>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DLL1 p.Arg207Ser (c.619C>A)?

AlphaMissense predicts likely benign (score 0.2239) — an in-silico prediction, not a clinical call.

DLL1 p.Arg207Ser

c.619C>A · rs761643780 · VCV2804449

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2239 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2239	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -7.03	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 0.77	GERP -3.7, phastCons 0.97
Regional constraint	o/e 0.66	unconstrained · MANE · 4,873 bp · p 2e-13 · regional, not allelic
Overall
CADD	15.81	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 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000753% 11/1,461,664 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
Admixed American	0.005%	20,009
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000169%	590,023

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: DLL1
Protein: p.Arg207Ser
Coding: c.619C>A
MANE Select: NM_005618
dbSNP: rs761643780
Type: single nucleotide variant
Location: chr6:170288290 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 207: the dsl domain; 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala564Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg168His Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg252Gln Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg430Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg502Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg502His Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg570Gln 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-arg207ser (accessed [today's date]).

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