Is DLL1 p.Ser711Pro (c.2131T>C) pathogenic?

DLL1 p.Ser711Pro (c.2131T>C) is classified Uncertain significance in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). AlphaMissense: likely pathogenic (0.6338); Very rare (popmax 0.00133%, afr); Associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures.

How common is DLL1 p.Ser711Pro (c.2131T>C) in the general population?

DLL1 p.Ser711Pro (c.2131T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DLL1 p.Ser711Pro (c.2131T>C)?

AlphaMissense predicts likely pathogenic (score 0.6338) — an in-silico prediction, not a clinical call.

DLL1 p.Ser711Pro

Q: What condition is associated with DLL1 p.Ser711Pro (c.2131T>C)?

DLL1 p.Ser711Pro (c.2131T>C) is associated with neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (ClinVar).

c.2131T>C · rs376347132 · VCV2688942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures

Computational evidence

Protein change
AlphaMissense	0.6338	likely pathogenic
REVEL	0.455	indeterminate
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,388 bp · p 0.59 · regional, not allelic
Overall
CADD	23.4	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

Grpmax group 0.00133% African / African-American · 1/74,930 alleles

Overall 0.000657% 1/152,188 alleles · very rare

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.Ser711Pro
Coding: c.2131T>C
MANE Select: NM_005618
dbSNP: rs376347132
Type: single nucleotide variant
Location: chr6:170283023 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 711: 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

Disease context

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLL1 p.Ser711= Benign/Likely benign ★★ same residue
DLL1 p.Arg509Ter Pathogenic ★★ same condition
DLL1 c.413-3T>G Uncertain significance ★★ same condition
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same condition
DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg176Cys Uncertain significance ★★ ⚠ same condition
DLL1 p.Arg392Cys 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-ser711pro (accessed [today's date]).

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