Is DPP9 p.Val601Met (c.1801G>A) pathogenic?

DPP9 p.Val601Met (c.1801G>A) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: ambiguous (0.4849); Ultra-rare (popmax 0.0172%, mid).

How common is DPP9 p.Val601Met (c.1801G>A) in the general population?

DPP9 p.Val601Met (c.1801G>A) is ultra-rare (popmax 0.0172%, mid) (gnomAD).

What do computational predictors say about DPP9 p.Val601Met (c.1801G>A)?

AlphaMissense predicts ambiguous (score 0.4849) — an in-silico prediction, not a clinical call.

DPP9 p.Val601Met

c.1801G>A · VCV3273662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4849	ambiguous
REVEL	0.223	benign-leaning
SaProt	LLR -9.45	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	29.1	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 V572M vs ClinVar V601M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0172% Middle Eastern · 1/5,798 alleles

Filtering AF 0.000787% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000624%

Overall 0.00139% 21/1,511,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0172%	5,798
African / African-American	0.00294%	34,038
South Asian	0.00267%	37,402
Remaining individualsnot grpmax-eligible	0.00172%	58,210
European (non-Finnish)	0.00131%	76,276

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.Val601Met
Coding: c.1801G>A
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4688841 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 601: a UniProt-annotated variant site (in hatis; likely pathogenic); an α-helix

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-val601met (accessed [today's date]).

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