Is DPP7 p.Gly49Asp (c.146G>A) pathogenic?

DPP7 p.Gly49Asp (c.146G>A) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: ambiguous (0.504); Ultra-rare (popmax 0.0206%, sas).

How common is DPP7 p.Gly49Asp (c.146G>A) in the general population?

DPP7 p.Gly49Asp (c.146G>A) is ultra-rare (popmax 0.0206%, sas) (gnomAD).

What do computational predictors say about DPP7 p.Gly49Asp (c.146G>A)?

AlphaMissense predicts ambiguous (score 0.504) — an in-silico prediction, not a clinical call.

DPP7 p.Gly49Asp

c.146G>A · VCV4014628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.504 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0206%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.504	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -7.35	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 6.7	GERP 0.96, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 416 bp · p 8.2e-05 · regional, not allelic
Overall
CADD	22.3	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 0.0206% South Asian · 18/87,498 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00168% 24/1,431,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0206%	4,861
Middle Eastern	0.0196%	5,106
Remaining individualsnot grpmax-eligible	0.0049%	20,389
European (non-Finnish)	0.000172%	582,747

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: DPP7
Protein: p.Gly49Asp
Coding: c.146G>A
MANE Select: NM_013379
Type: single nucleotide variant
Location: chr9:137114498 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 49: a turn

Full DPP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP7 p.Gly49Ser Uncertain significance ★ ⚠ same residue
DPP7 p.Arg17= Likely benign ★★ same type
DPP7 c.322-1G>T Uncertain significance ★ same type
DPP7 p.Ala118Gly Uncertain significance ★ ⚠ same type
DPP7 p.Ala118Val Uncertain significance ★ ⚠ same type
DPP7 p.Ala136Val Uncertain significance ★ ⚠ same type
DPP7 p.Ala139Gly Uncertain significance ★ ⚠ same type
DPP7 p.Ala13Val Uncertain significance ★ ⚠ 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/dpp7-p-gly49asp (accessed [today's date]).

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