Is DNPEP p.Ala263Ser (c.787G>T) pathogenic?

DNPEP p.Ala263Ser (c.787G>T) is classified Uncertain significance in DNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2284); Very rare (popmax 0.00441%, nfe).

How common is DNPEP p.Ala263Ser (c.787G>T) in the general population?

DNPEP p.Ala263Ser (c.787G>T) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about DNPEP p.Ala263Ser (c.787G>T)?

AlphaMissense predicts likely benign (score 0.2284) — an in-silico prediction, not a clinical call.

DNPEP p.Ala263Ser

c.787G>T · VCV3504272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2284	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -8.98	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 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.2 · regional, not allelic
Overall
CADD	24.4	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 0.00441% European (non-Finnish) · 52/1,178,702 alleles

Filtering AF 0.00343% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00329% 53/1,611,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00441%	22,667
Admixed American	0.00167%	59,752

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: DNPEP
Protein: p.Ala263Ser
Coding: c.787G>T
MANE Select: NM_012100
Type: single nucleotide variant
Location: chr2:219384431 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.95 · 1 PDB
Residue 263: a turn

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

Similar variants

DNPEP p.Tyr308Cys Uncertain significance ★★ ⚠ same type
DNPEP p.Ile171Val Benign ★★ same type
DNPEP p.Ala204Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala221Thr Uncertain significance ★ ⚠ same type
DNPEP p.Ala27Val Uncertain significance ★ ⚠ same type
DNPEP p.Ala321Ser Uncertain significance ★ ⚠ same type
DNPEP p.Arg114His Uncertain significance ★ ⚠ same type
DNPEP p.Arg114Leu 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/dnpep-p-ala263ser (accessed [today's date]).

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