Is NMBR p.Arg310Trp (c.928C>T) pathogenic?

NMBR p.Arg310Trp (c.928C>T) is classified Likely benign in NMBR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.7199); Rare (popmax 0.825%, mid).

How common is NMBR p.Arg310Trp (c.928C>T) in the general population?

NMBR p.Arg310Trp (c.928C>T) is rare (popmax 0.825%, mid) (gnomAD).

What do computational predictors say about NMBR p.Arg310Trp (c.928C>T)?

AlphaMissense predicts likely pathogenic (score 0.7199) — an in-silico prediction, not a clinical call.

NMBR p.Arg310Trp

c.928C>T · rs142626832 · VCV770365

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7199 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.825%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7199	likely pathogenic
REVEL	0.392	indeterminate
SaProt	LLR -10.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.88	GERP -2.8, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 13 kb · p 0.00021 · regional, not allelic
Overall
CADD	24.4	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 0.825% Middle Eastern · 50/6,062 alleles

Filtering AF 0.643% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.629%

Overall 0.556% 8,975/1,614,006 alleles · rare exomes 8,300/1,461,782 · genomes 675/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.825%	121
European (non-Finnish)	0.646%	155
Remaining individualsnot grpmax-eligible	0.603%	166
Admixed American	0.562%	178
Ashkenazi Jewishnot grpmax-eligible	0.443%	226
Finnishnot grpmax-eligible	0.259%	386
South Asian	0.234%	428
African / African-American	0.101%	987
East Asian	0.00446%	22,440

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: NMBR
Protein: p.Arg310Trp
Coding: c.928C>T
MANE Select: NM_002511
dbSNP: rs142626832
Type: single nucleotide variant
Location: chr6:142075893 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 2 PDB
Residue 310: an α-helix

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

Similar variants

NMBR p.Arg310Gln Uncertain significance ★ ⚠ same residue
NMBR p.Ile46= Benign/Likely benign ★★ same type
NMBR p.Ser358= Likely benign ★★ same type
NMBR p.Ala136Asp Uncertain significance ★ ⚠ same type
NMBR p.Ala179Val Uncertain significance ★ ⚠ same type
NMBR p.Ala185Val Uncertain significance ★ ⚠ same type
NMBR p.Ala236Thr Uncertain significance ★ ⚠ same type
NMBR p.Ala32Gly 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/nmbr-p-arg310trp (accessed [today's date]).

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