Is DUSP19 p.Ile136Thr (c.407T>C) pathogenic?

DUSP19 p.Ile136Thr (c.407T>C) is classified Uncertain significance in DUSP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.4717); Ultra-rare (popmax 0.0223%, nfe).

How common is DUSP19 p.Ile136Thr (c.407T>C) in the general population?

DUSP19 p.Ile136Thr (c.407T>C) is ultra-rare (popmax 0.0223%, nfe) (gnomAD).

What do computational predictors say about DUSP19 p.Ile136Thr (c.407T>C)?

AlphaMissense predicts ambiguous (score 0.4717) — an in-silico prediction, not a clinical call.

DUSP19 p.Ile136Thr

c.407T>C · VCV4015391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4717	ambiguous
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -14.10	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.9 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% European (non-Finnish) · 263/1,179,724 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0192%

Overall 0.0166% 268/1,612,656 alleles · ultra-rare exomes 258/1,460,450 · genomes 10/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0223%	4,486
Remaining individualsnot grpmax-eligible	0.00641%	15,606
African / African-American	0.00134%	74,892

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: DUSP19
Protein: p.Ile136Thr
Coding: c.407T>C
MANE Select: NM_080876
Type: single nucleotide variant
Location: chr2:183087173 (GRCh38)
Gene constraint: LOEUF 1.516 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.39 · 4 PDB
Residue 136: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP19 p.Ile136Val Uncertain significance ★ ⚠ same residue
DUSP19 p.Ala10Val Uncertain significance ★ ⚠ same type
DUSP19 p.Arg141Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198Cys Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198His Uncertain significance ★ ⚠ same type
DUSP19 p.Arg211Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Asn167Ser Uncertain significance ★ ⚠ same type
DUSP19 p.Asp143Gly 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/dusp19-p-ile136thr (accessed [today's date]).

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