Is DPP6 p.Asp76Val (c.227A>T) pathogenic?

DPP6 p.Asp76Val (c.227A>T) is classified Conflicting classifications of pathogenicity in DPP6 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2024-11-27). AlphaMissense: likely benign (0.1419); Low-frequency (popmax 2.89%, mid).

How common is DPP6 p.Asp76Val (c.227A>T) in the general population?

DPP6 p.Asp76Val (c.227A>T) is low-frequency (popmax 2.89%, mid) (gnomAD).

What do computational predictors say about DPP6 p.Asp76Val (c.227A>T)?

AlphaMissense predicts likely benign (score 0.1419) — an in-silico prediction, not a clinical call.

DPP6 p.Asp76Val

c.227A>T · rs572667303 · VCV252780

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1419 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.89%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1419	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 840 kb · p 1.6e-08 · regional, not allelic
Overall
CADD	20.2	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

Grpmax group 2.89% Middle Eastern · 70/2,426 alleles

Filtering AF 2.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.14%

Overall 1.43% 14,997/1,052,324 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.89%	35
Ashkenazi Jewishnot grpmax-eligible	2.83%	35
Admixed American	1.56%	64
European (non-Finnish)	1.55%	65
Remaining individualsnot grpmax-eligible	1.48%	67
South Asian	0.557%	180
Finnishnot grpmax-eligible	0.308%	325
African / African-American	0.268%	373
East Asian	0.00648%	15,432

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.Asp76Val
Coding: c.227A>T
MANE Select: NM_130797
dbSNP: rs572667303
Type: single nucleotide variant
Location: chr7:154053047 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 76: the 'disordered' region

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

Similar variants

DPP6 p.Asp76Asn Conflicting classifications of pathogenicity ★ ⚠ 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-asp76val (accessed [today's date]).

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