Is IDE p.Lys324Arg (c.971A>G) pathogenic?

IDE p.Lys324Arg (c.971A>G) is classified Uncertain significance in IDE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.093); Ultra-rare (popmax 0.0286%, sas).

How common is IDE p.Lys324Arg (c.971A>G) in the general population?

IDE p.Lys324Arg (c.971A>G) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

What do computational predictors say about IDE p.Lys324Arg (c.971A>G)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

IDE p.Lys324Arg

c.971A>G · rs572543538 · VCV3108017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 56 kb · p 4.3e-15 · regional, not allelic
Overall
CADD	22.1	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 0.0286% South Asian · 26/91,058 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00161% 26/1,613,152 alleles · ultra-rare exomes 23/1,460,808 · genomes 3/152,344 · 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: IDE
Protein: p.Lys324Arg
Coding: c.971A>G
MANE Select: NM_004969
dbSNP: rs572543538
Type: single nucleotide variant
Location: chr10:92508817 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 62 PDB
Residue 324: an α-helix

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

Similar variants

IDE p.Asn841= Benign ★★ same type
IDE p.His10= Benign/Likely benign ★★ same type
IDE p.Ile791= Benign ★★ same type
IDE p.Ala185Glu Uncertain significance ★ ⚠ same type
IDE p.Ala452Thr Uncertain significance ★ ⚠ same type
IDE p.Ala479Thr Uncertain significance ★ ⚠ same type
IDE p.Ala544Val Uncertain significance ★ ⚠ same type
IDE p.Ala610Val 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/ide-p-lys324arg (accessed [today's date]).

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