Is DLL1 p.Ser351Phe (c.1052C>T) pathogenic?

DLL1 p.Ser351Phe (c.1052C>T) is classified Uncertain significance in DLL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-31). AlphaMissense: likely benign (0.1907); Absent from gnomAD v4.1.

How common is DLL1 p.Ser351Phe (c.1052C>T) in the general population?

DLL1 p.Ser351Phe (c.1052C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLL1 p.Ser351Phe (c.1052C>T)?

AlphaMissense predicts likely benign (score 0.1907) — an in-silico prediction, not a clinical call.

DLL1 p.Ser351Phe

c.1052C>T · rs1353415684 · VCV1947882

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1907	likely benign
REVEL	0.578	indeterminate
SaProt	LLR -9.29	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 9.7	GERP -1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,388 bp · p 0.59 · regional, not allelic
Overall
CADD	29.2	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

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.Ser351Phe
Coding: c.1052C>T
MANE Select: NM_005618
dbSNP: rs1353415684
Type: single nucleotide variant
Location: chr6:170285116 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 351: a disulfide bond; a UniProt-annotated variant site (in nedbas); a β-strand; the egf-like 4; calcium-binding domain

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

Similar variants

DLL1 p.Ser351= Likely benign ★ 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-ser351phe (accessed [today's date]).

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