Is IDE p.Val271Leu (c.811G>T) pathogenic?

IDE p.Val271Leu (c.811G>T) is classified Uncertain significance in IDE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: ambiguous (0.5074); Ultra-rare (popmax 0.0288%, amr).

How common is IDE p.Val271Leu (c.811G>T) in the general population?

IDE p.Val271Leu (c.811G>T) is ultra-rare (popmax 0.0288%, amr) (gnomAD).

What do computational predictors say about IDE p.Val271Leu (c.811G>T)?

AlphaMissense predicts ambiguous (score 0.5074) — an in-silico prediction, not a clinical call.

IDE p.Val271Leu

c.811G>T · rs930851011 · VCV3108014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0288%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5074	ambiguous
REVEL	0.138	moderately benign-leaning
SaProt	LLR -13.11	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 64 kb · p 0.32 · regional, not allelic
Overall
CADD	23.4	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 0.0288% Admixed American · 17/59,070 alleles

Filtering AF 0.0183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00145% 23/1,588,244 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0288%	3,475
Remaining individualsnot grpmax-eligible	0.00975%	10,258

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.Val271Leu
Coding: c.811G>T
MANE Select: NM_004969
dbSNP: rs930851011
Type: single nucleotide variant
Location: chr10:92510136 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 62 PDB
Residue 271: 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-val271leu (accessed [today's date]).

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