Is DUSP16 p.Arg208His (c.623G>A) pathogenic?

DUSP16 p.Arg208His (c.623G>A) is classified Uncertain significance in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely pathogenic (0.9418); Very rare (popmax 0.00549%, sas).

How common is DUSP16 p.Arg208His (c.623G>A) in the general population?

DUSP16 p.Arg208His (c.623G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DUSP16 p.Arg208His (c.623G>A)?

AlphaMissense predicts likely pathogenic (score 0.9418) — an in-silico prediction, not a clinical call.

DUSP16 p.Arg208His

c.623G>A · rs370518275 · VCV2480066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9418	likely pathogenic
REVEL	0.447	indeterminate
SaProt	LLR -13.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 44 kb · p 0.0011 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00549% South Asian · 5/91,088 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00155% 25/1,614,042 alleles · very rare exomes 22/1,461,860 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Remaining individualsnot grpmax-eligible	0.0048%	20,830
African / African-American	0.00267%	37,457
Admixed American	0.00167%	60,008
Finnishnot grpmax-eligible	0.00156%	64,014
European (non-Finnish)	0.0011%	90,771

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.Arg208His
Coding: c.623G>A
MANE Select: NM_030640
dbSNP: rs370518275
Type: single nucleotide variant
Location: chr12:12487096 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 208: the tyrosine-protein phosphatase domain; a β-strand

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.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-arg208his (accessed [today's date]).

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