Is DPP8 p.Gln514Arg (c.1541A>G) pathogenic?

DPP8 p.Gln514Arg (c.1541A>G) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.0641); Very rare (popmax 0.00534%, afr).

How common is DPP8 p.Gln514Arg (c.1541A>G) in the general population?

DPP8 p.Gln514Arg (c.1541A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DPP8 p.Gln514Arg (c.1541A>G)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

DPP8 p.Gln514Arg

c.1541A>G · rs147909400 · VCV3085571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -2.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.77, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00056 · regional, not allelic
Overall
CADD	18.47	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q530R vs ClinVar Q514R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,894 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,724
Remaining individualsnot grpmax-eligible	0.0032%	31,239

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.Gln514Arg
Coding: c.1541A>G
MANE Select: NM_130434
dbSNP: rs147909400
Type: single nucleotide variant
Location: chr15:65467219 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB
Residue 514: a β-strand

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

Similar variants

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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-gln514arg (accessed [today's date]).

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