Is DONSON p.Gln428Ter (c.1282C>T) pathogenic?

DONSON p.Gln428Ter (c.1282C>T) is classified Pathogenic/Likely pathogenic in DONSON (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-24). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with DONSON p.Gln428Ter (c.1282C>T)?

DONSON p.Gln428Ter (c.1282C>T) is associated with Inborn genetic diseases, microcephaly-micromelia syndrome, microcephaly, short stature, and limb abnormalities (ClinVar).

How common is DONSON p.Gln428Ter (c.1282C>T) in the general population?

DONSON p.Gln428Ter (c.1282C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

DONSON p.Gln428Ter

c.1282C>T · rs993687029 · VCV431419

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

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 8 of 10
REVEL	0.484	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.8, phastCons 1
Overall
CADD	40.0	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 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000991% 16/1,614,024 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.0011%	90,771

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: DONSON
Protein: p.Gln428Ter
Coding: c.1282C>T
MANE Select: NM_017613
dbSNP: rs993687029
Type: single nucleotide variant
Location: chr21:33581370 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 428: a UniProt-annotated variant site (in missla)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly-micromelia syndrome microcephaly, short stature, and limb abnormalities

Similar variants

DONSON c.1047-9A>G Pathogenic ★★ same condition
DONSON c.1563+1G>T Pathogenic ★★ same condition
DONSON p.Arg442Ter Pathogenic ★★ same condition
DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ same condition
DONSON p.Ala32Gly Uncertain significance ★★ ⚠ same condition
DONSON p.Ala429Glu Uncertain significance ★★ ⚠ same condition
DONSON p.Arg162Gln Uncertain significance ★★ ⚠ same condition
DONSON p.Arg234His 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/donson-p-gln428ter (accessed [today's date]).

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