Is REN p.Ile386Val (c.1156A>G) pathogenic?

REN p.Ile386Val (c.1156A>G) is classified Uncertain significance in REN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.3394); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with REN p.Ile386Val (c.1156A>G)?

REN p.Ile386Val (c.1156A>G) is associated with Inborn genetic diseases (ClinVar).

How common is REN p.Ile386Val (c.1156A>G) in the general population?

REN p.Ile386Val (c.1156A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about REN p.Ile386Val (c.1156A>G)?

AlphaMissense predicts likely benign (score 0.3394) — an in-silico prediction, not a clinical call.

REN p.Ile386Val

c.1156A>G · VCV4629033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3394 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3394	likely benign
REVEL	0.346	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.2, phastCons 1
Overall
CADD	24.2	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

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: REN
Protein: p.Ile386Val
Coding: c.1156A>G
MANE Select: NM_001363642 · reported on NM_000537
Type: single nucleotide variant
Location: chr1:204155081 (GRCh38)
Structure: AlphaFold pLDDT 85.00

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

REN p.Lys139Ter Pathogenic ★★ same condition
REN p.Arg119His Uncertain significance ★★ ⚠ same condition
REN p.Arg399His Uncertain significance ★★ ⚠ same condition
REN p.Gln160Arg Uncertain significance ★★ ⚠ same condition
REN p.Glu253Lys Uncertain significance ★★ ⚠ same condition
REN p.Glu310Lys Uncertain significance ★★ ⚠ same condition
REN p.Glu89Lys Uncertain significance ★★ ⚠ same condition
REN p.Gly175Val Uncertain significance ★★ same condition

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/ren-p-ile386val (accessed [today's date]).

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