Is DPP10 p.Lys331Asn (c.993G>C) pathogenic?

DPP10 p.Lys331Asn (c.993G>C) is classified Uncertain significance in DPP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.4957); Very rare (popmax 6.85e-05%).

How common is DPP10 p.Lys331Asn (c.993G>C) in the general population?

DPP10 p.Lys331Asn (c.993G>C) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about DPP10 p.Lys331Asn (c.993G>C)?

AlphaMissense predicts ambiguous (score 0.4957) — an in-silico prediction, not a clinical call.

DPP10 p.Lys331Asn

c.993G>C · VCV4244458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4957	ambiguous
REVEL	0.208	benign-leaning
SaProt	LLR -8.12	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 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 103 kb · p 0.025 · regional, not allelic
Overall
CADD	25.3	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 6.85e-05%

Overall 6.85e-05% 1/1,459,802 alleles · very rare

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: DPP10
Protein: p.Lys331Asn
Coding: c.993G>C
MANE Select: NM_020868
Type: single nucleotide variant
Location: chr2:115753216 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.67 · 1 PDB
Residue 331: a β-strand

Full DPP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP10 p.Asp380= Benign ★★ same type
DPP10 p.Glu234Asp Benign ★★ ⚠ same type
DPP10 p.Gly601Ser Benign ★★ ⚠ same type
DPP10 p.His130= Likely benign ★★ same type
DPP10 p.Leu575= Benign ★★ same type
DPP10 c.852+1G>T Uncertain significance ★ same type
DPP10 p.Ala112Ser Uncertain significance ★ ⚠ same type
DPP10 p.Ala455Val 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/dpp10-p-lys331asn (accessed [today's date]).

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