Is RNLS p.Glu37Asp (c.111G>C) pathogenic?

RNLS p.Glu37Asp (c.111G>C) is classified Benign in RNLS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0964); Common (popmax 52.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with end stage renal failure.

What condition is associated with RNLS p.Glu37Asp (c.111G>C)?

RNLS p.Glu37Asp (c.111G>C) is associated with end stage renal failure (ClinVar).

What do computational predictors say about RNLS p.Glu37Asp (c.111G>C)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

RNLS p.Glu37Asp

Q: How common is RNLS p.Glu37Asp (c.111G>C) in the general population?

RNLS p.Glu37Asp (c.111G>C) is common (popmax 52.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.111G>C · rs2296545 · VCV1250700

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 52.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

end stage renal failure

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.21	GERP -2.2, phastCons 0.004
Regional constraint	o/e 0.99	unconstrained · MANE · 298 kb · p 0.87 · regional, not allelic
Overall
CADD	12.94	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 52.6% African / African-American · 39,282/74,698 alleles

Filtering AF 52.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 52%

Overall 44.3% 711,816/1,608,540 alleles · common exomes 640,025/1,456,380 · genomes 71,791/152,160 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	61.4%	2
Finnishnot grpmax-eligible	53.3%	2
African / African-Americangrpmax	52.6%	2
Middle Eastern	49.5%	2
Ashkenazi Jewishnot grpmax-eligible	47.8%	2
South Asian	46.4%	2
Admixed American	45.4%	2
Remaining individualsnot grpmax-eligible	44.8%	2
European (non-Finnish)	42.9%	2
East Asian	41.9%	2

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RNLS
Protein: p.Glu37Asp
Coding: c.111G>C
MANE Select: NM_001031709
dbSNP: rs2296545
Type: single nucleotide variant
Location: chr10:88583080 (GRCh38)

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

Disease context

end stage renal failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/rnls-p-glu37asp (accessed [today's date]).

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