Is DUSP16 p.Arg130His (c.389G>A) pathogenic?

DUSP16 p.Arg130His (c.389G>A) is classified Uncertain significance in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0664); Ultra-rare (popmax 0.0822%, eas).

How common is DUSP16 p.Arg130His (c.389G>A) in the general population?

DUSP16 p.Arg130His (c.389G>A) is ultra-rare (popmax 0.0822%, eas) (gnomAD).

What do computational predictors say about DUSP16 p.Arg130His (c.389G>A)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

DUSP16 p.Arg130His

c.389G>A · VCV3505846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 44 kb · p 0.0011 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% East Asian · 36/43,796 alleles

Filtering AF 0.061% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0537%

Overall 0.00383% 61/1,591,714 alleles · ultra-rare exomes 55/1,439,516 · genomes 6/152,198 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0822%	1,217
South Asian	0.00576%	17,347
Remaining individualsnot grpmax-eligible	0.00487%	20,534
Admixed American	0.00183%	54,706
African / African-American	0.00135%	73,822
European (non-Finnish)	0.00128%	78,116

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.Arg130His
Coding: c.389G>A
MANE Select: NM_030640
Type: single nucleotide variant
Location: chr12:12500661 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 130: the rhodanese domain; an α-helix

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.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
DUSP16 p.Arg611Gln 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-arg130his (accessed [today's date]).

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