Is DUSP16 p.Pro221= (c.663G>T) pathogenic?

DUSP16 p.Pro221= (c.663G>T) is classified Likely benign in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-04). Ultra-rare (popmax 0.0913%, eas).

How common is DUSP16 p.Pro221= (c.663G>T) in the general population?

DUSP16 p.Pro221= (c.663G>T) is ultra-rare (popmax 0.0913%, eas) (gnomAD).

DUSP16 p.Pro221=

c.663G>T · rs372821072 · VCV723986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0913%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Overall
CADD	0.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0913% East Asian · 41/44,886 alleles

Filtering AF 0.0692% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00576% 93/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0913%	1,095
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Admixed American	0.005%	20,007
European (non-Finnish)	0.000169%	589,988

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.Pro221=
Coding: c.663G>T
MANE Select: NM_030640
dbSNP: rs372821072
Type: single nucleotide variant
Location: chr12:12487056 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 221: the tyrosine-protein phosphatase domain

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

Similar variants

DUSP16 p.Ala2Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Ala358Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Ala73Val Uncertain significance ★ ⚠ same type
DUSP16 p.Arg130His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg14Lys Uncertain significance ★ ⚠ same type
DUSP16 p.Arg208His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg483Gln Uncertain significance ★ ⚠ same type
DUSP16 p.Arg598Cys Uncertain significance ★ ⚠ 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/dusp16-p-pro221 (accessed [today's date]).

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