Is NMRAL1 p.Arg37Gln (c.110G>A) pathogenic?

NMRAL1 p.Arg37Gln (c.110G>A) is classified Uncertain significance in NMRAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: ambiguous (0.5155); Ultra-rare (popmax 0.0153%, nfe).

How common is NMRAL1 p.Arg37Gln (c.110G>A) in the general population?

NMRAL1 p.Arg37Gln (c.110G>A) is ultra-rare (popmax 0.0153%, nfe) (gnomAD).

What do computational predictors say about NMRAL1 p.Arg37Gln (c.110G>A)?

AlphaMissense predicts ambiguous (score 0.5155) — an in-silico prediction, not a clinical call.

NMRAL1 p.Arg37Gln

c.110G>A · rs143521179 · VCV2560485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5155	ambiguous
REVEL	0.638	indeterminate
SaProt	LLR -12.82	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.16 · regional, not allelic
Overall
CADD	27.3	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 0.0153% European (non-Finnish) · 180/1,180,010 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0127% 205/1,614,114 alleles · ultra-rare exomes 187/1,461,868 · genomes 18/152,246 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0153%	6,556
African / African-American	0.0133%	7,503
Admixed American	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0096%	10,417
East Asian	0.00446%	22,436

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: NMRAL1
Protein: p.Arg37Gln
Coding: c.110G>A
MANE Select: NM_020677
dbSNP: rs143521179
Type: single nucleotide variant
Location: chr16:4469396 (GRCh38)
Gene constraint: LOEUF 1.471 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.67 · 5 PDB
Residue 37: a β-strand; a binding site

Full NMRAL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NMRAL1 p.Ala126Ser Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala127Thr Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala128Thr Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala43Thr Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala43Val Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala68Thr Uncertain significance ★ ⚠ same type
NMRAL1 p.Ala98Thr Uncertain significance ★ same type
NMRAL1 p.Arg141Gln 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/nmral1-p-arg37gln (accessed [today's date]).

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