Is DPP9 p.Ala323Val (c.968C>T) pathogenic?

DPP9 p.Ala323Val (c.968C>T) is classified Uncertain significance in DPP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-03). AlphaMissense: ambiguous (0.3489); Very rare (popmax 0.00446%, eas).

How common is DPP9 p.Ala323Val (c.968C>T) in the general population?

DPP9 p.Ala323Val (c.968C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DPP9 p.Ala323Val (c.968C>T)?

AlphaMissense predicts ambiguous (score 0.3489) — an in-silico prediction, not a clinical call.

DPP9 p.Ala323Val

c.968C>T · VCV4014656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3489	ambiguous
REVEL	0.278	benign-leaning
SaProt	LLR -4.15	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 6.7	GERP -0.44, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 34 kb · p 0.00027 · regional, not allelic
Overall
CADD	23.6	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 A294V vs ClinVar A323V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000889% 13/1,461,642 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000678%	147,482

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.Ala323Val
Coding: c.968C>T
MANE Select: NM_139159
Type: single nucleotide variant
Location: chr19:4702071 (GRCh38)
Gene constraint: LOEUF 0.647 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96 · 14 PDB
Residue 323: a UniProt-annotated variant site (in hatis; likely pathogenic); a β-strand

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-ala323val (accessed [today's date]).

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