Is DPP6 p.Gly630Ser (c.1888G>A) pathogenic?

DPP6 p.Gly630Ser (c.1888G>A) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00017%, nfe); Associated with intellectual disability, autosomal dominant 33.

What condition is associated with DPP6 p.Gly630Ser (c.1888G>A)?

DPP6 p.Gly630Ser (c.1888G>A) is associated with intellectual disability, autosomal dominant 33 (ClinVar).

How common is DPP6 p.Gly630Ser (c.1888G>A) in the general population?

DPP6 p.Gly630Ser (c.1888G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DPP6 p.Gly630Ser (c.1888G>A)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

DPP6 p.Gly630Ser

c.1888G>A · rs2150654585 · VCV1701761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, autosomal dominant 33

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.58	indeterminate
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	23.7	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 0.00017% European (non-Finnish) · 2/1,177,762 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,456,450 alleles · very rare

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.Gly630Ser
Coding: c.1888G>A
MANE Select: NM_130797
dbSNP: rs2150654585
Type: single nucleotide variant
Location: chr7:154875910 (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

Disease context

intellectual disability, autosomal dominant 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPP6 p.Lys223Arg Uncertain significance ★★ ⚠ same condition
DPP6 p.Pro229Thr Uncertain significance ★★ ⚠ same condition
DPP6 p.Gln271= Benign ★★ same condition
DPP6 p.Lys241= Benign ★★ same condition
DPP6 p.Arg775Ter Likely pathogenic ★ same condition
DPP6 p.Tyr205Ter Likely pathogenic ★ same condition
DPP6 c.2304+2T>C Uncertain significance ★ same condition
DPP6 c.457+3G>A Uncertain significance ★ 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-gly630ser (accessed [today's date]).

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