Is DPP6 p.Phe709= (c.2127T>C) pathogenic?

DPP6 p.Phe709= (c.2127T>C) is classified Benign in DPP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-11-17). Common (popmax 43.8%, afr) — too common for a highly-penetrant pathogenic allele.

DPP6 p.Phe709=

Q: How common is DPP6 p.Phe709= (c.2127T>C) in the general population?

DPP6 p.Phe709= (c.2127T>C) is common (popmax 43.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2127T>C · rs3817522 · VCV1296305

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 43.8%, afr) — 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 -9.6	GERP -2.9
Overall
CADD	0.664	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.8% African / African-American · 32,798/74,918 alleles

Filtering AF 43.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.2%

Overall 20.8% 335,095/1,613,582 alleles · common exomes 293,534/1,461,596 · genomes 41,561/151,986 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	43.8%	2
Admixed American	43.1%	2
Middle Eastern	25.8%	4
Finnishnot grpmax-eligible	24.1%	4
Remaining individualsnot grpmax-eligible	21.3%	5
Ashkenazi Jewishnot grpmax-eligible	19.9%	5
European (non-Finnish)	18.8%	5
South Asian	13.9%	7
East Asian	13.5%	7
Amishnot grpmax-eligible	13%	8

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.Phe709=
Coding: c.2127T>C
MANE Select: NM_130797
dbSNP: rs3817522
Type: single nucleotide variant
Location: chr7:154880936 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 709: 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-phe709 (accessed [today's date]).

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