Is DLL3 p.Gly313= (c.939G>A) pathogenic?

DLL3 p.Gly313= (c.939G>A) is classified Conflicting classifications of pathogenicity in DLL3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0269%, nfe); Associated with spondylocostal dysostosis 1, autosomal recessive.

What condition is associated with DLL3 p.Gly313= (c.939G>A)?

DLL3 p.Gly313= (c.939G>A) is associated with spondylocostal dysostosis 1, autosomal recessive, syndactyly (ClinVar).

How common is DLL3 p.Gly313= (c.939G>A) in the general population?

DLL3 p.Gly313= (c.939G>A) is ultra-rare (popmax 0.0269%, nfe) (gnomAD).

DLL3 p.Gly313=

c.939G>A · rs150100958 · VCV329235

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, nfe)

Conditions

spondylocostal dysostosis 1, autosomal recessive

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 1.1	GERP -3.7, phastCons 1
Overall
CADD	10.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0269% European (non-Finnish) · 317/1,180,036 alleles

Filtering AF 0.0244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0234%

Overall 0.021% 339/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0269%	3,723
Remaining individualsnot grpmax-eligible	0.024%	4,166
Admixed American	0.01%	10,001
African / African-American	0.00133%	74,930

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: DLL3
Protein: p.Gly313=
Coding: c.939G>A
MANE Select: NM_203486
dbSNP: rs150100958
Type: single nucleotide variant
Location: chr19:39505297 (GRCh38)
Gene constraint: LOEUF 1.512 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.42
Residue 313: the egf-like 3 domain

Full DLL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondylocostal dysostosis 1, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: syndactyly

Similar variants

DLL3 p.Gly313Arg Uncertain significance ★★ ⚠ same residue
DLL3 c.652+1G>T Likely pathogenic ★★ same condition
DLL3 p.Arg238Ter Pathogenic ★★ same condition
DLL3 p.Cys178Ter Likely pathogenic ★★ same condition
DLL3 p.Cys207Ter Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Cys379Tyr Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Gln346Ter Pathogenic/Likely pathogenic ★★ same condition
DLL3 p.Gly504Asp Pathogenic/Likely pathogenic ★★ 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/dll3-p-gly313 (accessed [today's date]).

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