Is DUSP16 p.Ile256= (c.768C>T) pathogenic?

DUSP16 p.Ile256= (c.768C>T) is classified Likely benign in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Low-frequency (popmax 1.19%, mid).

How common is DUSP16 p.Ile256= (c.768C>T) in the general population?

DUSP16 p.Ile256= (c.768C>T) is low-frequency (popmax 1.19%, mid) (gnomAD).

DUSP16 p.Ile256=

c.768C>T · rs61758451 · VCV2642739

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.19%, mid)

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 -2.1	GERP -3.7
Overall
CADD	6.557	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.19% Middle Eastern · 72/6,062 alleles

Filtering AF 0.967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.886%

Overall 0.633% 10,224/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.92%	52
Middle Easterngrpmax	1.19%	84
Remaining individualsnot grpmax-eligible	0.842%	119
South Asian	0.782%	128
European (non-Finnish)	0.667%	150
Admixed American	0.608%	164
African / African-American	0.0986%	1,014
Finnishnot grpmax-eligible	0.0625%	1,601

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile256=
Coding: c.768C>T
MANE Select: NM_030640
dbSNP: rs61758451
Type: single nucleotide variant
Location: chr12:12480270 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 256: the tyrosine-protein phosphatase 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.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-ile256 (accessed [today's date]).

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