Is DESI2 p.His30Arg (c.89A>G) pathogenic?

DESI2 p.His30Arg (c.89A>G) is classified Uncertain significance in DESI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1.

How common is DESI2 p.His30Arg (c.89A>G) in the general population?

DESI2 p.His30Arg (c.89A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DESI2 p.His30Arg (c.89A>G)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

DESI2 p.His30Arg

c.89A>G · rs2527186462 · VCV3081793

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 4% in DESI2
REVEL	0.815	moderately pathogenic-leaning
SaProt	LLR -10.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 5,283 bp · p 8.9e-10 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DESI2
Protein: p.His30Arg
Coding: c.89A>G
MANE Select: NM_016076
dbSNP: rs2527186462
Type: single nucleotide variant
Location: chr1:244686643 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 86.26
Residue 30: the pppde domain; an active site

Full DESI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DESI2 p.Ala153Ser Uncertain significance ★ ⚠ same type
DESI2 p.Ala153Thr Uncertain significance ★ ⚠ same type
DESI2 p.Ala175Thr Uncertain significance ★ ⚠ same type
DESI2 p.Arg126Cys Uncertain significance ★ ⚠ same type
DESI2 p.Arg126His Uncertain significance ★ ⚠ same type
DESI2 p.Arg190Cys Uncertain significance ★ ⚠ same type
DESI2 p.Asp172Asn Uncertain significance ★ ⚠ same type
DESI2 p.Glu123Asp 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/desi2-p-his30arg (accessed [today's date]).

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