Is REN p.Lys37= (c.111G>A) pathogenic?

REN p.Lys37= (c.111G>A) is classified Likely benign in REN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-13). Very rare (popmax 0.00178%, nfe); Associated with REN-related disorder.

What condition is associated with REN p.Lys37= (c.111G>A)?

REN p.Lys37= (c.111G>A) is associated with REN-related disorder (ClinVar).

How common is REN p.Lys37= (c.111G>A) in the general population?

REN p.Lys37= (c.111G>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

REN p.Lys37=

c.111G>A · rs1658258409 · VCV3031540

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

REN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Overall
CADD	14.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,036 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,614,038 alleles · very rare

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: REN
Protein: p.Lys37=
Coding: c.111G>A
MANE Select: NM_001363642 · reported on NM_000537
dbSNP: rs1658258409
Type: single nucleotide variant
Location: chr1:204162151 (GRCh38)
Structure: AlphaFold pLDDT 85.00
Residue 37: the btb domain

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

Disease context

REN-related disorder

Similar variants

REN p.Asp211Asn Uncertain significance ★★ same condition
REN c.961-5C>A Conflicting classifications of pathogenicity ★ same condition
REN p.Thr122Ala Uncertain significance ⚠ same condition
REN c.689+7A>G Likely benign same condition
REN p.Ile262fs Likely pathogenic ★ same condition
REN c.250-5dup Likely benign same condition
REN c.249+1G>A Pathogenic/Likely pathogenic ★★ same type
REN p.Arg49Ter Pathogenic/Likely pathogenic ★★ 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/ren-p-lys37 (accessed [today's date]).

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