Is DPP7 p.Ala21Thr (c.61G>A) pathogenic?

DPP7 p.Ala21Thr (c.61G>A) is classified Likely benign in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1205); Very rare (popmax 0.000282%, nfe).

How common is DPP7 p.Ala21Thr (c.61G>A) in the general population?

DPP7 p.Ala21Thr (c.61G>A) is very rare (popmax 0.000282%, nfe) (gnomAD).

What do computational predictors say about DPP7 p.Ala21Thr (c.61G>A)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

DPP7 p.Ala21Thr

c.61G>A · rs1276913359 · VCV2553527

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000282%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -10.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -1.8, phastCons 0.002
Regional constraint	o/e 1.35	unconstrained · MANE · 416 bp · p 8.2e-05 · regional, not allelic
Overall
CADD	7.808	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 0.000282% European (non-Finnish) · 3/1,065,444 alleles

Filtering AF 7.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.00116% 16/1,374,962 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.026%	3,843
European (non-Finnish)grpmax	0.000282%	355,148

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala21Thr
Coding: c.61G>A
MANE Select: NM_013379
dbSNP: rs1276913359
Type: single nucleotide variant
Location: chr9:137114653 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB

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

Similar variants

DPP7 p.Ala21Glu 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-ala21thr (accessed [today's date]).

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