Is DUSP18 p.Leu79Val (c.235C>G) pathogenic?

DUSP18 p.Leu79Val (c.235C>G) is classified Uncertain significance in DUSP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.3128); Very rare (popmax 0.000508%, nfe).

How common is DUSP18 p.Leu79Val (c.235C>G) in the general population?

DUSP18 p.Leu79Val (c.235C>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about DUSP18 p.Leu79Val (c.235C>G)?

AlphaMissense predicts likely benign (score 0.3128) — an in-silico prediction, not a clinical call.

DUSP18 p.Leu79Val

c.235C>G · rs756322739 · VCV2294449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3128	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 563 bp · p 0.42 · regional, not allelic
Overall
CADD	23.3	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 0.000508% European (non-Finnish) · 6/1,180,026 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,212 alleles · very rare exomes 6/1,461,892 · genomes 0/152,320 · joint denominator

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: DUSP18
Protein: p.Leu79Val
Coding: c.235C>G
MANE Select: NM_152511
dbSNP: rs756322739
Type: single nucleotide variant
Location: chr22:30663769 (GRCh38)

Full DUSP18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp18-p-leu79val (accessed [today's date]).

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