Is DPP6 p.Ser665= (c.1995C>T) pathogenic?

DPP6 p.Ser665= (c.1995C>T) is classified Likely benign in DPP6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-17). Ultra-rare (popmax 0.02%, amr); Associated with DPP6-related disorder.

What condition is associated with DPP6 p.Ser665= (c.1995C>T)?

DPP6 p.Ser665= (c.1995C>T) is associated with DPP6-related disorder (ClinVar).

How common is DPP6 p.Ser665= (c.1995C>T) in the general population?

DPP6 p.Ser665= (c.1995C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

DPP6 p.Ser665=

c.1995C>T · rs558465693 · VCV3041739

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

DPP6-related disorder

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 -5.5	GERP -3.4
Overall
CADD	7.975	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,978 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00465% 75/1,612,974 alleles · ultra-rare exomes 62/1,460,726 · genomes 13/152,248 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	4,998
African / African-American	0.0107%	9,376
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,791
Remaining individualsnot grpmax-eligible	0.00481%	20,809
European (non-Finnish)	0.00424%	23,592

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.Ser665=
Coding: c.1995C>T
MANE Select: NM_130797
dbSNP: rs558465693
Type: single nucleotide variant
Location: chr7:154876017 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 665: a β-strand

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

Disease context

DPP6-related disorder

Similar variants

DPP6 c.1299+68G>A Uncertain significance ★ same condition
DPP6 c.244-1G>A Uncertain significance ★ same condition
DPP6 p.Glu139Lys Uncertain significance ⚠ same condition
DPP6 p.His267Leu Uncertain significance ⚠ same condition
DPP6 p.Tyr205Asn Uncertain significance ⚠ same condition
DPP6 c.1299+179C>G Likely benign same condition
DPP6 c.1299+18G>A Likely benign same condition
DPP6 c.1299+51C>T Likely benign same condition

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-ser665 (accessed [today's date]).

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