Is DPP8 p.Ala18Val (c.53C>T) pathogenic?

DPP8 p.Ala18Val (c.53C>T) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely benign (0.1073); Ultra-rare (popmax 0.0164%, mid).

How common is DPP8 p.Ala18Val (c.53C>T) in the general population?

DPP8 p.Ala18Val (c.53C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DPP8 p.Ala18Val (c.53C>T)?

AlphaMissense predicts likely benign (score 0.1073) — an in-silico prediction, not a clinical call.

DPP8 p.Ala18Val

c.53C>T · VCV3504985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1073	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -5.54	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00056 · regional, not allelic
Overall
CADD	24.8	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 A34V vs ClinVar A18V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00161% 26/1,613,880 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00549%	18,217
African / African-American	0.00267%	37,439
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)	0.00136%	73,747

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.Ala18Val
Coding: c.53C>T
MANE Select: NM_130434
Type: single nucleotide variant
Location: chr15:65512501 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB

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.Ala374Gly 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-ala18val (accessed [today's date]).

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