Is DPP6 p.Val637= (c.1911G>A) pathogenic?

DPP6 p.Val637= (c.1911G>A) is classified Benign in DPP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-06). Common (popmax 36.5%, nfe) — too common for a highly-penetrant pathogenic allele.

DPP6 p.Val637=

Q: How common is DPP6 p.Val637= (c.1911G>A) in the general population?

DPP6 p.Val637= (c.1911G>A) is common (popmax 36.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1911G>A · rs2230064 · VCV1296304

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 36.5%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Overall
CADD	7.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.5% European (non-Finnish) · 430,724/1,178,766 alleles

Filtering AF 36.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.4%

Overall 32.6% 526,218/1,611,746 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	45.6%	2
European (non-Finnish)grpmax	36.5%	3
Finnishnot grpmax-eligible	31.7%	3
Remaining individualsnot grpmax-eligible	30%	3
Ashkenazi Jewishnot grpmax-eligible	26.7%	4
Middle Eastern	23.4%	4
South Asian	22.6%	4
Admixed American	20.2%	5
African / African-American	17.7%	6
East Asian	2.22%	45

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val637=
Coding: c.1911G>A
MANE Select: NM_130797
dbSNP: rs2230064
Type: single nucleotide variant
Location: chr7:154875933 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB

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-val637 (accessed [today's date]).

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