Is DPP3 p.Ala69Thr (c.205G>A) pathogenic?

DPP3 p.Ala69Thr (c.205G>A) is classified Uncertain significance in DPP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.0785); Very rare (popmax 0.00549%, sas).

How common is DPP3 p.Ala69Thr (c.205G>A) in the general population?

DPP3 p.Ala69Thr (c.205G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DPP3 p.Ala69Thr (c.205G>A)?

AlphaMissense predicts likely benign (score 0.0785) — an in-silico prediction, not a clinical call.

DPP3 p.Ala69Thr

c.205G>A · VCV4661968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0785	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 27 kb · p 1e-05 · regional, not allelic
Overall
CADD	18.37	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,088 alleles

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

Overall 0.00186% 30/1,610,494 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Admixed American	0.005%	20,007
East Asian	0.00446%	22,440
European (non-Finnish)	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ala69Thr
Coding: c.205G>A
MANE Select: NM_130443
Type: single nucleotide variant
Location: chr11:66482405 (GRCh38)
Gene constraint: LOEUF 0.827 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.56 · 10 PDB
Residue 69: 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-ala69thr (accessed [today's date]).

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