Is DPP6 p.Cys660Tyr (c.1979G>A) pathogenic?

DPP6 p.Cys660Tyr (c.1979G>A) is classified Uncertain significance in DPP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: ambiguous (0.3477); Absent from gnomAD v4.1.

How common is DPP6 p.Cys660Tyr (c.1979G>A) in the general population?

DPP6 p.Cys660Tyr (c.1979G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPP6 p.Cys660Tyr (c.1979G>A)?

AlphaMissense predicts ambiguous (score 0.3477) — an in-silico prediction, not a clinical call.

DPP6 p.Cys660Tyr

c.1979G>A · rs2486918918 · VCV3027026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3477	ambiguous
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.59, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPP6
Protein: p.Cys660Tyr
Coding: c.1979G>A
MANE Select: NM_130797
dbSNP: rs2486918918
Type: single nucleotide variant
Location: chr7:154876001 (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-cys660tyr (accessed [today's date]).

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