Is NMRAL1 p.Asn80Ser (c.239A>G) pathogenic?

NMRAL1 p.Asn80Ser (c.239A>G) is classified Uncertain significance in NMRAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.1459); Very rare (popmax 0.004%, afr).

How common is NMRAL1 p.Asn80Ser (c.239A>G) in the general population?

NMRAL1 p.Asn80Ser (c.239A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about NMRAL1 p.Asn80Ser (c.239A>G)?

AlphaMissense predicts likely benign (score 0.1459) — an in-silico prediction, not a clinical call.

NMRAL1 p.Asn80Ser

c.239A>G · rs146163636 · VCV2209680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1459	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.85, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.16 · regional, not allelic
Overall
CADD	24.0	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 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00105% 17/1,614,002 alleles · very rare exomes 15/1,461,844 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,974
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00102%	98,334

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.Asn80Ser
Coding: c.239A>G
MANE Select: NM_020677
dbSNP: rs146163636
Type: single nucleotide variant
Location: chr16:4469267 (GRCh38)
Gene constraint: LOEUF 1.471 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.67 · 5 PDB
Residue 80: 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-asn80ser (accessed [today's date]).

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