Is DPP6 p.Gly65Val (c.194G>T) pathogenic?

DPP6 p.Gly65Val (c.194G>T) is classified Uncertain significance in DPP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-01). AlphaMissense: likely benign (0.1196); Very rare (popmax 0.00621%, eas).

How common is DPP6 p.Gly65Val (c.194G>T) in the general population?

DPP6 p.Gly65Val (c.194G>T) is very rare (popmax 0.00621%, eas) (gnomAD).

What do computational predictors say about DPP6 p.Gly65Val (c.194G>T)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

DPP6 p.Gly65Val

c.194G>T · rs879255430 · VCV252779

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00621%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -8.43	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 6.5	GERP 2.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	20.6	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 0.00621% East Asian · 1/16,098 alleles

Filtering AF 0.000332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.000756% 8/1,057,564 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00621%	16,098
European (non-Finnish)	0.000799%	125,217

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.Gly65Val
Coding: c.194G>T
MANE Select: NM_130797
dbSNP: rs879255430
Type: single nucleotide variant
Location: chr7:154053014 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 65: the 'disordered' region

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

Similar variants

DPP6 p.Gly65Cys Uncertain significance ★★ ⚠ same residue
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
DPP6 c.1300-100C>T 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-gly65val (accessed [today's date]).

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