Is DLL1 p.Pro678= (c.2034G>A) pathogenic?

DLL1 p.Pro678= (c.2034G>A) is classified Likely benign in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). Very rare (popmax 0.004%, afr).

How common is DLL1 p.Pro678= (c.2034G>A) in the general population?

DLL1 p.Pro678= (c.2034G>A) is very rare (popmax 0.004%, afr) (gnomAD).

DLL1 p.Pro678=

c.2034G>A · rs776288082 · VCV2969612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -3.4
Overall
CADD	2.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,914 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00112% 18/1,612,482 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,971
Admixed American	0.00334%	29,974
East Asian	0.00223%	44,864
European (non-Finnish)	0.00102%	98,320

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.Pro678=
Coding: c.2034G>A
MANE Select: NM_005618
dbSNP: rs776288082
Type: single nucleotide variant
Location: chr6:170283245 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 678: the 'disordered' region; a UniProt-annotated variant site (in nedbas); a UniProt-annotated variant site (in nedbas; uncertain significance)

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

Similar variants

DLL1 p.Pro678Ala Uncertain significance ★ ⚠ same residue
DLL1 p.Pro678Leu Uncertain significance ★ ⚠ same residue
DLL1 p.Arg509Ter Pathogenic ★★ same type
DLL1 c.413-3T>G Uncertain significance ★★ same type
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same type
DLL1 p.Ala371Val Uncertain significance ★★ ⚠ same type
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same type
DLL1 p.Ala550Thr 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/dll1-p-pro678 (accessed [today's date]).

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