Is DUSP15 p.Pro129Ser (c.385C>T) pathogenic?

DUSP15 p.Pro129Ser (c.385C>T) is classified Uncertain significance in DUSP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: ambiguous (0.5431); Very rare (popmax 0.00237%, nfe).

How common is DUSP15 p.Pro129Ser (c.385C>T) in the general population?

DUSP15 p.Pro129Ser (c.385C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about DUSP15 p.Pro129Ser (c.385C>T)?

AlphaMissense predicts ambiguous (score 0.5431) — an in-silico prediction, not a clinical call.

DUSP15 p.Pro129Ser

c.385C>T · VCV4245497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5431	ambiguous
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.49	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 12	GERP 1.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,931 bp · p 0.015 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P126S vs ClinVar P129S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,002 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,613,996 alleles · very rare exomes 27/1,461,784 · genomes 2/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,143
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: DUSP15
Protein: p.Pro129Ser
Coding: c.385C>T
MANE Select: NM_080611
Type: single nucleotide variant
Location: chr20:31862621 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.61 · 1 PDB
Residue 126 UniProt numbering: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP15 p.Ala191Pro Uncertain significance ★ same type
DUSP15 p.Ala192Pro Uncertain significance ★ same type
DUSP15 p.Arg148Gln Uncertain significance ★ same type
DUSP15 p.Arg166Ser Uncertain significance ★ same type
DUSP15 p.Arg174Cys Uncertain significance ★ same type
DUSP15 p.Arg174His Uncertain significance ★ same type
DUSP15 p.Arg176Pro Uncertain significance ★ same type
DUSP15 p.Arg176Trp 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/dusp15-p-pro129ser (accessed [today's date]).

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