Is DONSON p.Ile382fs (c.1142dup) pathogenic?

DONSON p.Ile382fs (c.1142dup) is classified Pathogenic in DONSON (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-06). Very rare (popmax 0.00333%, amr).

How common is DONSON p.Ile382fs (c.1142dup) in the general population?

DONSON p.Ile382fs (c.1142dup) is very rare (popmax 0.00333%, amr) (gnomAD).

DONSON p.Ile382fs

c.1142dup · rs1247764954 · VCV1936222

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.6	GERP -7.8
Overall
CADD	34.0	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 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,970 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: DONSON
Protein: p.Ile382fs
Coding: c.1142dup
MANE Select: NM_017613
dbSNP: rs1247764954
Type: Duplication
Location: chr21:33581959 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.94
Residue 382: a UniProt-annotated variant site (in missla)

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

Similar variants

DONSON p.Ile382Met Uncertain significance ★ ⚠ same residue
DONSON p.Ile382Val Uncertain significance ★ ⚠ same residue
DONSON p.Lys419Ter Pathogenic/Likely pathogenic ★★ same type
DONSON p.Leu49fs Pathogenic ★ same type
DONSON p.Pro15fs Pathogenic ★ same type
DONSON p.Ser363fs Pathogenic ★ same type
DONSON p.Ser497fs Pathogenic ★ same type
DONSON c.1047-20dup Likely benign ★ 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/donson-p-ile382fs (accessed [today's date]).

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