Is DLL1 p.Phe543= (c.1629C>T) pathogenic?

DLL1 p.Phe543= (c.1629C>T) is classified Likely benign in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-21). Very rare (popmax 0.00102%, nfe).

How common is DLL1 p.Phe543= (c.1629C>T) in the general population?

DLL1 p.Phe543= (c.1629C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

DLL1 p.Phe543=

c.1629C>T · rs375849681 · VCV2415407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 1.4	GERP -2.7, phastCons 1
Overall
CADD	6.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,172,040 alleles

Filtering AF 0.000546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000431%

Overall 0.000899% 13/1,446,168 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,780
European (non-Finnish)grpmax	0.00102%	97,670

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe543=
Coding: c.1629C>T
MANE Select: NM_005618
dbSNP: rs375849681
Type: single nucleotide variant
Location: chr6:170283650 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 543: 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.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
DLL1 p.Arg168His 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-phe543 (accessed [today's date]).

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