Is DPP3 p.Leu183Ser (c.548T>C) pathogenic?

DPP3 p.Leu183Ser (c.548T>C) is classified Uncertain significance in DPP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.3077); Ultra-rare (popmax 0.0406%, sas).

How common is DPP3 p.Leu183Ser (c.548T>C) in the general population?

DPP3 p.Leu183Ser (c.548T>C) is ultra-rare (popmax 0.0406%, sas) (gnomAD).

What do computational predictors say about DPP3 p.Leu183Ser (c.548T>C)?

AlphaMissense predicts likely benign (score 0.3077) — an in-silico prediction, not a clinical call.

DPP3 p.Leu183Ser

c.548T>C · VCV4661962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3077 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3077	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -11.47	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 27 kb · p 1e-05 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0406% South Asian · 37/91,080 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.00341% 55/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,462
East Asian	0.0312%	3,206
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000254%	393,314

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: DPP3
Protein: p.Leu183Ser
Coding: c.548T>C
MANE Select: NM_130443
Type: single nucleotide variant
Location: chr11:66487317 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.56 · 10 PDB
Residue 183: an α-helix

Full DPP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP3 p.Arg76His Benign ★★ ⚠ same type
DPP3 p.Leu163Met Benign ★★ ⚠ same type
DPP3 p.Lys423= Benign ★★ same type
DPP3 p.Phe331= Benign ★★ same type
DPP3 p.Phe443= Benign ★★ same type
DPP3 p.Thr401= Benign ★★ same type
DPP3 c.573+1G>A Uncertain significance ★ same type
DPP3 p.Ala22Gly 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/dpp3-p-leu183ser (accessed [today's date]).

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