Is DUSP1 p.Val343Ile (c.1027G>A) pathogenic?

DUSP1 p.Val343Ile (c.1027G>A) is classified Uncertain significance in DUSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-15). AlphaMissense: likely benign (0.1835); Ultra-rare (popmax 0.0137%, sas).

How common is DUSP1 p.Val343Ile (c.1027G>A) in the general population?

DUSP1 p.Val343Ile (c.1027G>A) is ultra-rare (popmax 0.0137%, sas) (gnomAD).

What do computational predictors say about DUSP1 p.Val343Ile (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

DUSP1 p.Val343Ile

c.1027G>A · VCV3842874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 175 bp · p 0.69 · regional, not allelic
Overall
CADD	26.2	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 0.0137% South Asian · 12/87,700 alleles

Filtering AF 0.00788% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00614%

Overall 0.00395% 63/1,595,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0137%	7,308
Remaining individualsnot grpmax-eligible	0.00486%	20,580
African / African-American	0.00402%	24,896
European (non-Finnish)	0.00368%	27,210
Admixed American	0.0034%	29,400

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.Val343Ile
Coding: c.1027G>A
MANE Select: NM_004417
Type: single nucleotide variant
Location: chr5:172768839 (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-val343ile (accessed [today's date]).

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