Is DUSP16 p.Pro361fs (c.1080_1083del) pathogenic?

DUSP16 p.Pro361fs (c.10801083del) is classified Benign in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 24.5%, eas) — too common for a highly-penetrant pathogenic allele.

How common is DUSP16 p.Pro361fs (c.1080_1083del) in the general population?

DUSP16 p.Pro361fs (c.1080_1083del) is common (popmax 24.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

DUSP16 p.Pro361fs

c.1080_1083del · rs200271649 · VCV771457

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Common

common (popmax 24.5%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -2.4
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GCACGCTGG simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.5% East Asian · 11,002/44,844 alleles

Filtering AF 24.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 24%

Overall 2.35% 37,865/1,613,570 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	24.5%	4
South Asian	12.4%	8
Admixed American	11.7%	9
Remaining individualsnot grpmax-eligible	3.27%	31
Finnishnot grpmax-eligible	2.71%	37
Ashkenazi Jewishnot grpmax-eligible	1.43%	70
Middle Eastern	0.776%	129
African / African-American	0.368%	272
European (non-Finnish)	0.339%	295

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: DUSP16
Protein: p.Pro361fs
Coding: c.1080_1083del
MANE Select: NM_030640
dbSNP: rs200271649
Type: Deletion
Location: chr12:12477748 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 361: the 'disordered' region

Full DUSP16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp16-p-pro361fs (accessed [today's date]).

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