Is DPP7 p.Phe48Ser (c.143T>C) pathogenic?

DPP7 p.Phe48Ser (c.143T>C) is classified Uncertain significance in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.2878); Very rare (popmax 0.00876%, amr).

How common is DPP7 p.Phe48Ser (c.143T>C) in the general population?

DPP7 p.Phe48Ser (c.143T>C) is very rare (popmax 0.00876%, amr) (gnomAD).

What do computational predictors say about DPP7 p.Phe48Ser (c.143T>C)?

AlphaMissense predicts likely benign (score 0.2878) — an in-silico prediction, not a clinical call.

DPP7 p.Phe48Ser

c.143T>C · rs776741394 · VCV2402599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00876%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2878	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.05	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 4.6	GERP 0.96, phastCons 1
Regional constraint	o/e 1.35	unconstrained · MANE · 416 bp · p 8.2e-05 · regional, not allelic
Overall
CADD	19.32	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00876% Admixed American · 5/57,056 alleles

Filtering AF 0.00339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00216%

Overall 0.00183% 29/1,584,100 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00876%	11,411
European (non-Finnish)	0.00189%	53,006
Remaining individualsnot grpmax-eligible	0.00164%	61,150
African / African-American	0.00136%	73,528

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.Phe48Ser
Coding: c.143T>C
MANE Select: NM_013379
dbSNP: rs776741394
Type: single nucleotide variant
Location: chr9:137114501 (GRCh38)
Gene constraint: LOEUF 1.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.44 · 3 PDB
Residue 48: a turn

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-phe48ser (accessed [today's date]).

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