Is DONSON p.Leu49fs (c.129_144dup) pathogenic?

DONSON p.Leu49fs (c.129144dup) is classified Pathogenic in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). Absent from gnomAD; Associated with microcephaly, short stature, and limb abnormalities.

What condition is associated with DONSON p.Leu49fs (c.129_144dup)?

DONSON p.Leu49fs (c.129_144dup) is associated with microcephaly, short stature, and limb abnormalities (ClinVar).

How common is DONSON p.Leu49fs (c.129_144dup) in the general population?

DONSON p.Leu49fs (c.129_144dup) is absent from gnomAD (gnomAD).

DONSON p.Leu49fs

c.129_144dup · rs2517484685 · VCV2572996

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

microcephaly, short stature, and limb abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 1, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DONSON
Protein: p.Leu49fs
Coding: c.129_144dup
MANE Select: NM_017613
dbSNP: rs2517484685
Type: Duplication
Location: chr21:33588497 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 49: the 'disordered' region

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

Disease context

microcephaly, short stature, and limb abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DONSON p.Lys419Ter Pathogenic/Likely pathogenic ★★ same condition
DONSON c.1047-9A>G Pathogenic ★★ same condition
DONSON c.1563+1G>T Pathogenic ★★ same condition
DONSON p.Gln428Ter Pathogenic/Likely pathogenic ★★ same condition
DONSON p.Phe165Ser Pathogenic/Likely pathogenic ★★ same condition
DONSON p.Ile307Val Uncertain significance ★★ ⚠ same condition
DONSON p.Asn417_Ser418del Likely pathogenic ★ same condition
DONSON p.Gln101Ter 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/donson-p-leu49fs (accessed [today's date]).

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