Is DUSP10 p.Leu423Val (c.1267T>G) pathogenic?

DUSP10 p.Leu423Val (c.1267T>G) is classified Uncertain significance in DUSP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: ambiguous (0.4821); Very rare (popmax 8.47e-05%, nfe).

How common is DUSP10 p.Leu423Val (c.1267T>G) in the general population?

DUSP10 p.Leu423Val (c.1267T>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DUSP10 p.Leu423Val (c.1267T>G)?

AlphaMissense predicts ambiguous (score 0.4821) — an in-silico prediction, not a clinical call.

DUSP10 p.Leu423Val

c.1267T>G · VCV4662497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4821	ambiguous
REVEL	0.688	pathogenic-leaning
SaProt	LLR -8.53	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 37 kb · p 0.0053 · regional, not allelic
Overall
CADD	20.2	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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: DUSP10
Protein: p.Leu423Val
Coding: c.1267T>G
MANE Select: NM_007207
Type: single nucleotide variant
Location: chr1:221702594 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 70.95 · 23 PDB
Residue 423: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP10 p.Leu423Met Uncertain significance ★ ⚠ same residue
DUSP10 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala300Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala47Val Uncertain significance ★ ⚠ same type
DUSP10 p.Ala55Pro Uncertain significance ★ ⚠ same type
DUSP10 p.Ala99Ser Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Gln Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Trp 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/dusp10-p-leu423val (accessed [today's date]).

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