Is DPP9 p.Leu262Pro (c.785T>C) pathogenic?

DPP9 p.Leu262Pro (c.785T>C) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1342); Ultra-rare (popmax 0.0149%, afr).

How common is DPP9 p.Leu262Pro (c.785T>C) in the general population?

DPP9 p.Leu262Pro (c.785T>C) is ultra-rare (popmax 0.0149%, afr) (gnomAD).

What do computational predictors say about DPP9 p.Leu262Pro (c.785T>C)?

AlphaMissense predicts likely benign (score 0.1342) — an in-silico prediction, not a clinical call.

DPP9 p.Leu262Pro

c.785T>C · VCV3505006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1342 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1342	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -10.78	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 6.1	GERP -0.32, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	20.4	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 L233P vs ClinVar L262P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0149% African / African-American · 11/73,842 alleles

Filtering AF 0.00827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00642%

Overall 0.000879% 14/1,592,518 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0149%	6,713
East Asian	0.00683%	14,636

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: DPP9
Protein: p.Leu262Pro
Coding: c.785T>C
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4702701 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 262: a UniProt-annotated variant site (in hatis; likely pathogenic)

Full DPP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP9 p.Asp310Asn Uncertain significance ★★ ⚠ same type
DPP9 p.Lys509Arg Uncertain significance ★★ ⚠ same type
DPP9 p.Thr301Met Uncertain significance ★★ ⚠ same type
DPP9 p.Ala184Gly Benign/Likely benign ★★ same type
DPP9 p.Glu566Lys Benign/Likely benign ★★ ⚠ same type
DPP9 p.His83= Benign/Likely benign ★★ same type
DPP9 p.Pro322= Benign ★★ same type
DPP9 p.Ser236Asn Likely benign ★★ 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/dpp9-p-leu262pro (accessed [today's date]).

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