Is DUSP28 p.Leu172Ser (c.515T>C) pathogenic?

DUSP28 p.Leu172Ser (c.515T>C) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.087); Absent from gnomAD v4.1.

How common is DUSP28 p.Leu172Ser (c.515T>C) in the general population?

DUSP28 p.Leu172Ser (c.515T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP28 p.Leu172Ser (c.515T>C)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

DUSP28 p.Leu172Ser

c.515T>C · rs2536160169 · VCV2248131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -0.55
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	7.343	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP28
Protein: p.Leu172Ser
Coding: c.515T>C
MANE Select: NM_001370465
dbSNP: rs2536160169
Type: single nucleotide variant
Location: chr2:240561451 (GRCh38)
Gene constraint: LOEUF 1.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.88 · 2 PDB

Full DUSP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP28 p.Ala129Pro Uncertain significance ★ ⚠ same type
DUSP28 p.Ala136Ser Uncertain significance ★ ⚠ same type
DUSP28 p.Cys114Tyr Uncertain significance ★ ⚠ same type
DUSP28 p.Gln131Arg Uncertain significance ★ ⚠ same type
DUSP28 p.Glu154Gln Uncertain significance ★ ⚠ same type
DUSP28 p.Glu155Ala Uncertain significance ★ ⚠ same type
DUSP28 p.Leu150Phe Uncertain significance ★ ⚠ same type
DUSP28 p.Leu163Pro 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/dusp28-p-leu172ser (accessed [today's date]).

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