Is DLL3 p.Glu71Ter (c.211G>T) pathogenic?

DLL3 p.Glu71Ter (c.211G>T) is classified Pathogenic in DLL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-03). Very rare (popmax 0.00136%, afr).

How common is DLL3 p.Glu71Ter (c.211G>T) in the general population?

DLL3 p.Glu71Ter (c.211G>T) is very rare (popmax 0.00136%, afr) (gnomAD).

DLL3 p.Glu71Ter

c.211G>T · rs1243748540 · VCV2919568

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.95, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,424 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000194% 3/1,548,566 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,424
European (non-Finnish)	0.000174%	576,136

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: DLL3
Protein: p.Glu71Ter
Coding: c.211G>T
MANE Select: NM_203486
dbSNP: rs1243748540
Type: single nucleotide variant
Location: chr19:39499333 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42

Full DLL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLL3 c.652+1G>T Likely pathogenic ★★ same type
DLL3 p.Arg221Ter Pathogenic ★★ same type
DLL3 p.Arg238Ter Pathogenic ★★ same type
DLL3 p.Cys178Ter Likely pathogenic ★★ same type
DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same type
DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same type
DLL3 p.Gln346Ter Pathogenic/Likely pathogenic ★★ same type
DLL3 p.Gly504Asp Pathogenic/Likely pathogenic ★★ 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/dll3-p-glu71ter (accessed [today's date]).

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