Is DUSP1 p.Thr336Ile (c.1007C>T) pathogenic?

DUSP1 p.Thr336Ile (c.1007C>T) is classified Uncertain significance in DUSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.525); Ultra-rare (popmax 0.0599%, sas).

How common is DUSP1 p.Thr336Ile (c.1007C>T) in the general population?

DUSP1 p.Thr336Ile (c.1007C>T) is ultra-rare (popmax 0.0599%, sas) (gnomAD).

What do computational predictors say about DUSP1 p.Thr336Ile (c.1007C>T)?

AlphaMissense predicts ambiguous (score 0.525) — an in-silico prediction, not a clinical call.

DUSP1 p.Thr336Ile

c.1007C>T · VCV4662490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.525 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0599%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.525	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -8.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 175 bp · p 0.69 · regional, not allelic
Overall
CADD	22.9	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 0.0599% South Asian · 54/90,102 alleles

Filtering AF 0.0471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0426%

Overall 0.00348% 56/1,607,634 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0599%	1,669
Remaining individualsnot grpmax-eligible	0.00161%	62,238
European (non-Finnish)	8.5e-05%	1,176,114

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: DUSP1
Protein: p.Thr336Ile
Coding: c.1007C>T
MANE Select: NM_004417
Type: single nucleotide variant
Location: chr5:172768859 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 4 PDB

Full DUSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP1 p.Ala103Val Uncertain significance ★ ⚠ same type
DUSP1 p.Ala113Gly Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala202Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala59Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala69Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala92Asp 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/dusp1-p-thr336ile (accessed [today's date]).

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