Is NBAS p.Pro2102Arg (c.6305C>G) pathogenic?

NBAS p.Pro2102Arg (c.6305C>G) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1634); Ultra-rare (popmax 0.0373%, afr); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Pro2102Arg (c.6305C>G)?

NBAS p.Pro2102Arg (c.6305C>G) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Pro2102Arg (c.6305C>G) in the general population?

NBAS p.Pro2102Arg (c.6305C>G) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

What do computational predictors say about NBAS p.Pro2102Arg (c.6305C>G)?

AlphaMissense predicts likely benign (score 0.1634) — an in-silico prediction, not a clinical call.

NBAS p.Pro2102Arg

c.6305C>G · rs137987698 · VCV1477304

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1634 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1634	likely benign
REVEL	0.501	indeterminate
SaProt	LLR -4.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	26.1	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 0.0373% African / African-American · 28/75,066 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00192% 31/1,614,254 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,681
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000169%	590,026

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: NBAS
Protein: p.Pro2102Arg
Coding: c.6305C>G
MANE Select: NM_015909
dbSNP: rs137987698
Type: single nucleotide variant
Location: chr2:15218900 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 2102: a UniProt-annotated variant site (in ilfs2; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced protein expression levels in fibroblasts); a UniProt-annotated variant site (found in a patient with a multisystem disease involving liver, eye, immune system, connective tissue and bone; uncertain significance; reduced collagen secretion; diffuse collagen bundles; reduced protein expression in fibroblasts); the 'interaction with zw10 and rint1' region

Full NBAS 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

NBAS p.Pro2102Leu Uncertain significance ★★ ⚠ same residue
NBAS p.Pro2102= Likely benign ★★ same residue
NBAS p.Ala1568Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1645Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1795Val Uncertain significance ★★ ⚠ same condition
NBAS p.Ala1941Gly Uncertain significance ★★ ⚠ same condition
NBAS p.Ala195Thr Uncertain significance ★★ ⚠ same condition
NBAS p.Ala2005Thr 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/nbas-p-pro2102arg (accessed [today's date]).

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