Is DPP7 p.Ala95Pro (c.283G>C) pathogenic?

DPP7 p.Ala95Pro (c.283G>C) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-25). AlphaMissense: likely pathogenic (0.9192); Very rare (popmax 0.00335%, amr).

How common is DPP7 p.Ala95Pro (c.283G>C) in the general population?

DPP7 p.Ala95Pro (c.283G>C) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about DPP7 p.Ala95Pro (c.283G>C)?

AlphaMissense predicts likely pathogenic (score 0.9192) — an in-silico prediction, not a clinical call.

DPP7 p.Ala95Pro

c.283G>C · VCV4244520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9192	likely pathogenic
REVEL	0.511	indeterminate
SaProt	LLR -16.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 289 bp · p 0.0003 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00335% Admixed American · 2/59,634 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000561% 9/1,603,060 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,817
European (non-Finnish)	0.000595%	167,986

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.Ala95Pro
Coding: c.283G>C
MANE Select: NM_013379
Type: single nucleotide variant
Location: chr9:137114281 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 95: an α-helix

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

Similar variants

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
DPP7 p.Ala158Asp 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-ala95pro (accessed [today's date]).

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