Is DPP4 p.Asp331His (c.991G>C) pathogenic?

DPP4 p.Asp331His (c.991G>C) is classified Uncertain significance in DPP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.1397); Very rare (popmax 0.01%, amr).

How common is DPP4 p.Asp331His (c.991G>C) in the general population?

DPP4 p.Asp331His (c.991G>C) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DPP4 p.Asp331His (c.991G>C)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

DPP4 p.Asp331His

c.991G>C · rs760571427 · VCV2387131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.416	indeterminate
SaProt	LLR -10.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.8
Regional constraint	o/e 1.01	unconstrained · MANE · 81 kb · p 0.82 · regional, not allelic
Overall
CADD	11.6	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 0.01% Admixed American · 6/60,026 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,910 alleles · very rare exomes 6/1,461,580 · genomes 0/152,330 · joint denominator

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: DPP4
Protein: p.Asp331His
Coding: c.991G>C
MANE Select: NM_001935
dbSNP: rs760571427
Type: single nucleotide variant
Location: chr2:162024836 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.45 · 121 PDB
Residue 331: a β-strand

Full DPP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP4 c.1987+4T>C Benign ★★ same type
DPP4 p.Ala16= Benign ★★ same type
DPP4 p.Gly645= Benign ★★ same type
DPP4 p.Leu27= Benign ★★ same type
DPP4 p.Lys539= Likely benign ★★ same type
DPP4 p.Ser437Thr Benign ★★ same type
DPP4 p.Val266Ile Likely benign ★★ same type
DPP4 p.Ala654Thr 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/dpp4-p-asp331his (accessed [today's date]).

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