Is DPP10 p.Arg87Trp (c.259C>T) pathogenic?

DPP10 p.Arg87Trp (c.259C>T) is classified Uncertain significance in DPP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.1436); Ultra-rare (popmax 0.052%, amr).

How common is DPP10 p.Arg87Trp (c.259C>T) in the general population?

DPP10 p.Arg87Trp (c.259C>T) is ultra-rare (popmax 0.052%, amr) (gnomAD).

What do computational predictors say about DPP10 p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely benign (score 0.1436) — an in-silico prediction, not a clinical call.

DPP10 p.Arg87Trp

c.259C>T · rs577846336 · VCV2508863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1436 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1436	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -10.96	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.17, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,247 kb · p 0.078 · regional, not allelic
Overall
CADD	26.5	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 0.052% Admixed American · 31/59,630 alleles

Filtering AF 0.0376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0327%

Overall 0.00441% 71/1,610,268 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.052%	1,924
Middle Eastern	0.0165%	6,050
East Asian	0.00672%	14,880
Remaining individualsnot grpmax-eligible	0.00481%	20,777
South Asian	0.00332%	30,156
European (non-Finnish)	0.00255%	39,269

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: DPP10
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_020868
dbSNP: rs577846336
Type: single nucleotide variant
Location: chr2:115343900 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.67 · 1 PDB

Full DPP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP10 p.Arg87Gln Uncertain significance ★ ⚠ same residue
DPP10 p.Asp380= Benign ★★ same type
DPP10 p.Glu234Asp Benign ★★ same type
DPP10 p.Gly601Ser Benign ★★ same type
DPP10 p.His130= Likely benign ★★ same type
DPP10 p.Leu575= Benign ★★ same type
DPP10 c.852+1G>T Uncertain significance ★ same type
DPP10 p.Ala112Ser 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/dpp10-p-arg87trp (accessed [today's date]).

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