Is DPP6 p.Ala314Thr (c.940G>A) pathogenic?

DPP6 p.Ala314Thr (c.940G>A) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). AlphaMissense: ambiguous (0.4116); Very rare (popmax 0.00551%, nfe).

How common is DPP6 p.Ala314Thr (c.940G>A) in the general population?

DPP6 p.Ala314Thr (c.940G>A) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about DPP6 p.Ala314Thr (c.940G>A)?

AlphaMissense predicts ambiguous (score 0.4116) — an in-silico prediction, not a clinical call.

DPP6 p.Ala314Thr

c.940G>A · rs778166866 · VCV3026390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4116	ambiguous
REVEL	0.57	indeterminate
SaProt	LLR -9.56	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	26.4	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 0.00551% European (non-Finnish) · 65/1,179,758 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.0044% 71/1,613,308 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,150
East Asian	0.00223%	44,858
South Asian	0.0022%	45,503
Admixed American	0.00167%	59,956
Remaining individualsnot grpmax-eligible	0.0016%	62,424
African / African-American	0.00134%	74,816

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.Ala314Thr
Coding: c.940G>A
MANE Select: NM_130797
dbSNP: rs778166866
Type: single nucleotide variant
Location: chr7:154769473 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 314: a β-strand

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

Similar variants

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
DPP6 c.1299+200A>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-ala314thr (accessed [today's date]).

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