Is DPP8 p.Leu634Phe (c.1900C>T) pathogenic?

DPP8 p.Leu634Phe (c.1900C>T) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-30). AlphaMissense: likely benign (0.2311); Very rare (popmax 0.00221%, nfe).

How common is DPP8 p.Leu634Phe (c.1900C>T) in the general population?

DPP8 p.Leu634Phe (c.1900C>T) is very rare (popmax 0.00221%, nfe) (gnomAD).

What do computational predictors say about DPP8 p.Leu634Phe (c.1900C>T)?

AlphaMissense predicts likely benign (score 0.2311) — an in-silico prediction, not a clinical call.

DPP8 p.Leu634Phe

c.1900C>T · rs369179039 · VCV2380402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2311	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -10.74	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 0.91	GERP -0.18, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 17 kb · p 6.4e-15 · regional, not allelic
Overall
CADD	15.37	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 L650F vs ClinVar L634F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,177,768 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,609,948 alleles · very rare

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: DPP8
Protein: p.Leu634Phe
Coding: c.1900C>T
MANE Select: NM_130434
dbSNP: rs369179039
Type: single nucleotide variant
Location: chr15:65463832 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB
Residue 634: a β-strand

Full DPP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP8 p.Thr182Met Uncertain significance ★★ ⚠ same type
DPP8 p.Thr227Ser Uncertain significance ★★ ⚠ same type
DPP8 c.1017+1G>T Uncertain significance ★ same type
DPP8 c.259+1G>C Uncertain significance ★ same type
DPP8 c.-12+1811G>T Uncertain significance ★ ⚠ same type
DPP8 c.-12+1828C>T Uncertain significance ★ ⚠ same type
DPP8 p.Ala110Thr Uncertain significance ★ ⚠ same type
DPP8 p.Ala18Val 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/dpp8-p-leu634phe (accessed [today's date]).

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