Is DPEP2 p.Arg432His (c.1295G>A) pathogenic?

DPEP2 p.Arg432His (c.1295G>A) is classified Likely benign in DPEP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0986%, afr).

How common is DPEP2 p.Arg432His (c.1295G>A) in the general population?

DPEP2 p.Arg432His (c.1295G>A) is ultra-rare (popmax 0.0986%, afr) (gnomAD).

What do computational predictors say about DPEP2 p.Arg432His (c.1295G>A)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

DPEP2 p.Arg432His

c.1295G>A · rs200614898 · VCV2590632

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -5.96	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 -7.4	GERP -3.4
Regional constraint	o/e 0.96	unconstrained · MANE · 5,703 bp · p 0.27 · regional, not allelic
Overall
CADD	0.088	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 0.0986% African / African-American · 74/75,030 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0739%

Overall 0.00632% 102/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0986%	1,014
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.008%	12,501
South Asian	0.00659%	15,181
European (non-Finnish)	0.000932%	107,275

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: DPEP2
Protein: p.Arg432His
Coding: c.1295G>A
MANE Select: NM_022355
dbSNP: rs200614898
Type: single nucleotide variant
Location: chr16:67987672 (GRCh38)
Gene constraint: LOEUF 1.089 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.94

Full DPEP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP2 p.Ala226Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala276Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala33Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala59Thr Uncertain significance ★ ⚠ same type
DPEP2 p.Ala78Val Uncertain significance ★ ⚠ same type
DPEP2 p.Arg147Cys Uncertain significance ★ ⚠ same type
DPEP2 p.Arg147His Uncertain significance ★ ⚠ same type
DPEP2 p.Arg158Cys 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/dpep2-p-arg432his (accessed [today's date]).

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