Is NMRAL1 p.Asp238Asn (c.712G>A) pathogenic?

NMRAL1 p.Asp238Asn (c.712G>A) is classified Uncertain significance in NMRAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1395); Very rare (popmax 0.0028%, nfe).

How common is NMRAL1 p.Asp238Asn (c.712G>A) in the general population?

NMRAL1 p.Asp238Asn (c.712G>A) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about NMRAL1 p.Asp238Asn (c.712G>A)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

NMRAL1 p.Asp238Asn

c.712G>A · rs768408070 · VCV3200837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.9
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.16 · regional, not allelic
Overall
CADD	4.956	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

Grpmax group 0.0028% European (non-Finnish) · 33/1,179,878 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00223% 36/1,613,174 alleles · very rare exomes 36/1,460,804 · genomes 0/152,370 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,754
Remaining individualsnot grpmax-eligible	0.0016%	62,468
Finnishnot grpmax-eligible	0.00157%	63,608
South Asian	0.0011%	90,988

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.Asp238Asn
Coding: c.712G>A
MANE Select: NM_020677
dbSNP: rs768408070
Type: single nucleotide variant
Location: chr16:4463668 (GRCh38)
Gene constraint: LOEUF 1.471 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.67 · 5 PDB
Residue 238: a β-strand

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-asp238asn (accessed [today's date]).

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