Is NBEA p.Ser40Arg (c.118A>C) pathogenic?

NBEA p.Ser40Arg (c.118A>C) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.2626); Very rare (popmax 0.00144%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBEA p.Ser40Arg (c.118A>C)?

NBEA p.Ser40Arg (c.118A>C) is associated with Inborn genetic diseases (ClinVar).

How common is NBEA p.Ser40Arg (c.118A>C) in the general population?

NBEA p.Ser40Arg (c.118A>C) is very rare (popmax 0.00144%, afr) (gnomAD).

What do computational predictors say about NBEA p.Ser40Arg (c.118A>C)?

AlphaMissense predicts likely benign (score 0.2626) — an in-silico prediction, not a clinical call.

NBEA p.Ser40Arg

c.118A>C · rs765235867 · VCV2496466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2626	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -1.4
Regional constraint	o/e 1.34	unconstrained · MANE · 171 bp · p 0.0012 · regional, not allelic
Overall
CADD	18.3	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% African / African-American · 1/69,544 alleles

Overall 0.000128% 2/1,561,046 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,238
African / African-Americangrpmax	0.00144%	69,544

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: NBEA
Protein: p.Ser40Arg
Coding: c.118A>C
MANE Select: NM_001385012
dbSNP: rs765235867
Type: single nucleotide variant
Location: chr13:34942938 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NBEA p.Ser40Gly Likely benign ★★ same residue
NBEA p.Ser40Thr Uncertain significance ★ ⚠ same residue
NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same condition
NBEA p.Arg1325Gln Uncertain significance ★★ same condition
NBEA p.Arg2277Gln Uncertain significance ★★ same condition
NBEA p.Arg2291Gly Uncertain significance ★★ ⚠ same condition
NBEA p.Asp701Glu Uncertain significance ★★ ⚠ same condition
NBEA p.Gln2141Arg Uncertain significance ★★ ⚠ 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/nbea-p-ser40arg (accessed [today's date]).

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