Is DLD p.Gln25Ter (c.73C>T) pathogenic?

DLD p.Gln25Ter (c.73C>T) is classified Uncertain significance in DLD (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-15). Very rare (popmax 8.48e-05%, nfe); Associated with DLD-related disorder.

What condition is associated with DLD p.Gln25Ter (c.73C>T)?

DLD p.Gln25Ter (c.73C>T) is associated with DLD-related disorder (ClinVar).

How common is DLD p.Gln25Ter (c.73C>T) in the general population?

DLD p.Gln25Ter (c.73C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DLD p.Gln25Ter

c.73C>T · rs2535560917 · VCV3032685

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

DLD-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,724 alleles

Overall 6.84e-05% 1/1,461,204 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: DLD
Protein: p.Gln25Ter
Coding: c.73C>T
MANE Select: NM_000108
dbSNP: rs2535560917
Type: single nucleotide variant
Location: chr7:107893233 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB

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

Disease context

DLD-related disorder

Similar variants

DLD p.Gln25Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
DLD p.Asp479Val Pathogenic/Likely pathogenic ★★ same condition
DLD p.Glu375Lys Pathogenic/Likely pathogenic ★★ same condition
DLD p.Gly229Cys Pathogenic/Likely pathogenic ★★ same condition
DLD p.Thr194Met Uncertain significance ★★ ⚠ same condition
DLD c.1464+1G>A Pathogenic/Likely pathogenic ★★ same type
DLD c.198+1G>T Likely pathogenic ★★ same type
DLD c.39+1G>A Likely pathogenic ★★ 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/dld-p-gln25ter (accessed [today's date]).

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