Is DPP8 p.Phe815Leu (c.2445C>G) pathogenic?

DPP8 p.Phe815Leu (c.2445C>G) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.8914); Very rare (popmax 0.0067%, eas).

How common is DPP8 p.Phe815Leu (c.2445C>G) in the general population?

DPP8 p.Phe815Leu (c.2445C>G) is very rare (popmax 0.0067%, eas) (gnomAD).

What do computational predictors say about DPP8 p.Phe815Leu (c.2445C>G)?

AlphaMissense predicts likely pathogenic (score 0.8914) — an in-silico prediction, not a clinical call.

DPP8 p.Phe815Leu

c.2445C>G · VCV4244540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8914 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8914	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 17 kb · p 6.4e-15 · regional, not allelic
Overall
CADD	23.0	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 F831L vs ClinVar F815L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,778 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000205% 3/1,460,510 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.Phe815Leu
Coding: c.2445C>G
MANE Select: NM_130434
Type: single nucleotide variant
Location: chr15:65451080 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB
Residue 815: an α-helix

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-phe815leu (accessed [today's date]).

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