Is DPP6 p.Ser777= (c.2331C>T) pathogenic?

DPP6 p.Ser777= (c.2331C>T) is classified Likely benign in DPP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-05). Rare (popmax 0.189%, afr).

How common is DPP6 p.Ser777= (c.2331C>T) in the general population?

DPP6 p.Ser777= (c.2331C>T) is rare (popmax 0.189%, afr) (gnomAD).

DPP6 p.Ser777=

c.2331C>T · rs184591023 · VCV3024876

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.189%, afr)

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 -16	GERP -2.6
Overall
CADD	0.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% African / African-American · 142/74,956 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.0555% 895/1,613,072 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.189%	528
Remaining individualsnot grpmax-eligible	0.0816%	1,225
European (non-Finnish)	0.0584%	1,712
Admixed American	0.0167%	5,992
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,546
South Asian	0.00221%	45,329

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.Ser777=
Coding: c.2331C>T
MANE Select: NM_130797
dbSNP: rs184591023
Type: single nucleotide variant
Location: chr7:154889298 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 777: a disulfide bond

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

Similar variants

DPP6 p.Ser777Phe 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-ser777 (accessed [today's date]).

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