Is DPP6 p.Pro43Ala (c.127C>G) pathogenic?

DPP6 p.Pro43Ala (c.127C>G) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0575); Very rare (popmax 0.00164%, nfe).

How common is DPP6 p.Pro43Ala (c.127C>G) in the general population?

DPP6 p.Pro43Ala (c.127C>G) is very rare (popmax 0.00164%, nfe) (gnomAD).

What do computational predictors say about DPP6 p.Pro43Ala (c.127C>G)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

DPP6 p.Pro43Ala

c.127C>G · rs1401359876 · VCV1335703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00164%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.97	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 0.58	GERP 0.63, phastCons 0.23
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	14.68	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00164% European (non-Finnish) · 16/977,488 alleles

Filtering AF 0.000969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000784%

Overall 0.00156% 17/1,088,254 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00164%	61,093
African / African-American	0.00158%	63,210

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: DPP6
Protein: p.Pro43Ala
Coding: c.127C>G
MANE Select: NM_130797
dbSNP: rs1401359876
Type: single nucleotide variant
Location: chr7:154052947 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 43: the 'disordered' region

Full DPP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP6 p.Pro43Ser Uncertain significance same residue
DPP6 p.Gly65Cys Uncertain significance ★★ ⚠ same type
DPP6 p.Gly65Val Uncertain significance ★★ ⚠ same type
DPP6 p.Lys223Arg Uncertain significance ★★ ⚠ same type
DPP6 p.Pro229Thr Uncertain significance ★★ ⚠ same type
DPP6 c.1261-188G>A Benign ★★ same type
DPP6 c.1261-48G>A Benign ★★ same type
DPP6 c.1299+147A>G Benign ★★ 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/dpp6-p-pro43ala (accessed [today's date]).

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