Is DPP8 p.Thr182Met (c.545C>T) pathogenic?

DPP8 p.Thr182Met (c.545C>T) is classified Uncertain significance in DPP8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-04). AlphaMissense: likely benign (0.1305); Ultra-rare (popmax 0.0165%, mid).

How common is DPP8 p.Thr182Met (c.545C>T) in the general population?

DPP8 p.Thr182Met (c.545C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DPP8 p.Thr182Met (c.545C>T)?

AlphaMissense predicts likely benign (score 0.1305) — an in-silico prediction, not a clinical call.

DPP8 p.Thr182Met

c.545C>T · rs200120025 · VCV2386902

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1305 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1305	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -10.39	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00056 · regional, not allelic
Overall
CADD	24.3	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 T198M vs ClinVar T182M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00539% 87/1,613,380 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0297%	3,368
Middle Easterngrpmax	0.0165%	6,060
Admixed American	0.0133%	7,497
Remaining individualsnot grpmax-eligible	0.0064%	15,619
European (non-Finnish)	0.00458%	21,842
South Asian	0.0011%	91,060

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr182Met
Coding: c.545C>T
MANE Select: NM_130434
dbSNP: rs200120025
Type: single nucleotide variant
Location: chr15:65500607 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 19 PDB
Residue 182: a β-strand

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

Similar variants

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
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-thr182met (accessed [today's date]).

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