Is NBEA p.Arg203Pro (c.608G>C) pathogenic?

NBEA p.Arg203Pro (c.608G>C) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-26). AlphaMissense: likely pathogenic (0.9828); Very rare (popmax 8.49e-05%, nfe).

How common is NBEA p.Arg203Pro (c.608G>C) in the general population?

NBEA p.Arg203Pro (c.608G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about NBEA p.Arg203Pro (c.608G>C)?

AlphaMissense predicts likely pathogenic (score 0.9828) — an in-silico prediction, not a clinical call.

NBEA p.Arg203Pro

c.608G>C · VCV4687045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.9828	likely pathogenic
REVEL	0.361	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 107 kb · p 5.9e-10 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,914 alleles

Overall 6.21e-05% 1/1,609,846 alleles · very rare exomes 1/1,457,656 · genomes 0/152,190 · joint denominator

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.Arg203Pro
Coding: c.608G>C
MANE Select: NM_001385012
Type: single nucleotide variant
Location: chr13:35045028 (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

Similar variants

NBEA p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg145Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg2213Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Arg2866Ter Pathogenic ★★ same type
NBEA p.Arg696Ter Pathogenic/Likely pathogenic ★★ same type
NBEA p.Asp319Tyr Likely pathogenic ★★ same type
NBEA c.4242+5G>A Uncertain significance ★★ same type
NBEA p.Ala603Val 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/nbea-p-arg203pro (accessed [today's date]).

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