Is DLL1 p.Pro95Ser (c.283C>T) pathogenic?

DLL1 p.Pro95Ser (c.283C>T) is classified Uncertain significance in DLL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1182); Ultra-rare (popmax 0.0196%, amr); Associated with DLL1-related disorder.

What condition is associated with DLL1 p.Pro95Ser (c.283C>T)?

DLL1 p.Pro95Ser (c.283C>T) is associated with DLL1-related disorder (ClinVar).

How common is DLL1 p.Pro95Ser (c.283C>T) in the general population?

DLL1 p.Pro95Ser (c.283C>T) is ultra-rare (popmax 0.0196%, amr) (gnomAD).

What do computational predictors say about DLL1 p.Pro95Ser (c.283C>T)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

DLL1 p.Pro95Ser

c.283C>T · rs779478084 · VCV2172121

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DLL1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.479	indeterminate
SaProt	LLR -6.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -1.9, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 4,873 bp · p 2e-13 · regional, not allelic
Overall
CADD	24.0	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 0.0196% Admixed American · 10/50,962 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00809%

Overall 0.00169% 26/1,535,350 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0196%	5,096
Remaining individualsnot grpmax-eligible	0.00667%	14,985
European (non-Finnish)	0.00105%	95,539

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.Pro95Ser
Coding: c.283C>T
MANE Select: NM_005618
dbSNP: rs779478084
Type: single nucleotide variant
Location: chr6:170289580 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 95: a UniProt-annotated variant site (in nedbas)

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

Disease context

DLL1-related disorder

Similar variants

DLL1 p.Pro95= Likely benign same residue
DLL1 p.Gly475Asp Uncertain significance ★★ ⚠ same condition
DLL1 p.Val709Phe Uncertain significance ★★ ⚠ same condition
DLL1 p.Gln270Ter Likely pathogenic ★ same condition
DLL1 p.Pro261Leu Uncertain significance ★ ⚠ same condition
DLL1 p.Thr587Met Conflicting classifications of pathogenicity ★ ⚠ same condition
DLL1 p.Cys325Ter Likely pathogenic same condition
DLL1 p.Gly669Ala 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-pro95ser (accessed [today's date]).

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