Is NBEA p.Pro2242Ser (c.6724C>T) pathogenic?

NBEA p.Pro2242Ser (c.6724C>T) is classified Uncertain significance in NBEA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-21). AlphaMissense: likely benign (0.1748); Very rare (popmax 0.00017%, nfe).

How common is NBEA p.Pro2242Ser (c.6724C>T) in the general population?

NBEA p.Pro2242Ser (c.6724C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about NBEA p.Pro2242Ser (c.6724C>T)?

AlphaMissense predicts likely benign (score 0.1748) — an in-silico prediction, not a clinical call.

NBEA p.Pro2242Ser

c.6724C>T · rs2153013060 · VCV1698362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1748 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1748	likely benign
REVEL	0.294	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 202 kb · p 0.00013 · regional, not allelic
Overall
CADD	24.0	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 0.00017% European (non-Finnish) · 2/1,175,432 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,607,768 alleles · very rare exomes 2/1,455,666 · genomes 0/152,102 · 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.Pro2242Ser
Coding: c.6724C>T
MANE Select: NM_001385012
dbSNP: rs2153013060
Type: single nucleotide variant
Location: chr13:35550950 (GRCh38)
Gene constraint: LOEUF 0.137 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2242: the beach-type ph domain; a UniProt-annotated variant site (in nedege); a UniProt-annotated variant site (in nedege; uncertain significance)

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

Similar variants

NBEA p.Pro2242Ala Uncertain significance ★★ ⚠ same residue
NBEA p.Pro2242= Likely benign ★ same residue
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

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-pro2242ser (accessed [today's date]).

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