Is DPP8 p.Val542Ile (c.1624G>A) pathogenic?

DPP8 p.Val542Ile (c.1624G>A) is classified Uncertain significance in DPP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.02%, eas).

How common is DPP8 p.Val542Ile (c.1624G>A) in the general population?

DPP8 p.Val542Ile (c.1624G>A) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about DPP8 p.Val542Ile (c.1624G>A)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

DPP8 p.Val542Ile

c.1624G>A · rs780061945 · VCV3085573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.59	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 0.24	GERP -1, phastCons 0.003
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00056 · regional, not allelic
Overall
CADD	12.68	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 V558I vs ClinVar V542I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% East Asian · 9/44,888 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00161% 26/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,988
Admixed American	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00133%	74,922
South Asian	0.0011%	91,090
European (non-Finnish)	0.000593%	168,576

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.Val542Ile
Coding: c.1624G>A
MANE Select: NM_130434
dbSNP: rs780061945
Type: single nucleotide variant
Location: chr15:65467136 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB
Residue 542: 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-val542ile (accessed [today's date]).

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