Is NRL p.Arg147= (c.441G>A) pathogenic?

NRL p.Arg147= (c.441G>A) is classified Benign/Likely benign in NRL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.772%, nfe); Associated with retinitis pigmentosa.

What condition is associated with NRL p.Arg147= (c.441G>A)?

NRL p.Arg147= (c.441G>A) is associated with retinitis pigmentosa (ClinVar).

How common is NRL p.Arg147= (c.441G>A) in the general population?

NRL p.Arg147= (c.441G>A) is rare (popmax 0.772%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NRL p.Arg147=

c.441G>A · rs201197984 · VCV312941

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.772%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -0.48, phastCons 1
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.772% European (non-Finnish) · 9,082/1,176,132 alleles

Filtering AF 0.759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.753%

Overall 0.619% 9,916/1,602,306 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.772%	130
Remaining individualsnot grpmax-eligible	0.616%	162
South Asian	0.19%	528
Finnishnot grpmax-eligible	0.188%	532
Admixed American	0.128%	784
African / African-American	0.116%	861
Middle Eastern	0.0997%	1,003
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,314

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: NRL
Protein: p.Arg147=
Coding: c.441G>A
MANE Select: NM_001354768
dbSNP: rs201197984
Type: single nucleotide variant
Location: chr14:24081509 (GRCh38)
Gene constraint: LOEUF 1.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.42
Residue 147: a UniProt-annotated variant site (in escs2; likely pathogenic)

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

NRL p.Arg147Trp Uncertain significance ★ ⚠ same residue
NRL c.*813G>A Uncertain significance ★★ same condition
NRL p.Ala136Val Uncertain significance ★★ ⚠ same condition
NRL p.Ala76Val Uncertain significance ★★ ⚠ same condition
NRL p.Val142Ala Uncertain significance ★★ ⚠ same condition
NRL c.*113C>A Likely benign ★★ same condition
NRL c.*221G>A Benign ★★ same condition
NRL c.*834G>C Benign ★★ 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/nrl-p-arg147 (accessed [today's date]).

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