Is DLL1 p.Pro73Ala (c.217C>G) pathogenic?

DLL1 p.Pro73Ala (c.217C>G) is classified Uncertain significance in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: likely benign (0.2171); Absent from gnomAD v4.1.

How common is DLL1 p.Pro73Ala (c.217C>G) in the general population?

DLL1 p.Pro73Ala (c.217C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLL1 p.Pro73Ala (c.217C>G)?

AlphaMissense predicts likely benign (score 0.2171) — an in-silico prediction, not a clinical call.

DLL1 p.Pro73Ala

c.217C>G · rs2483363208 · VCV3252535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2171 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2171	likely benign
REVEL	0.751	pathogenic-leaning
SaProt	LLR -8.30	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 4,873 bp · p 2e-13 · regional, not allelic
Overall
CADD	28.6	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.Pro73Ala
Coding: c.217C>G
MANE Select: NM_005618
dbSNP: rs2483363208
Type: single nucleotide variant
Location: chr6:170289646 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 73: a UniProt-annotated variant site (in nedbas)

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

Similar variants

DLL1 p.Pro73Leu 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
DLL1 p.Ala564Thr 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-pro73ala (accessed [today's date]).

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