Is NBAS p.Arg1236Pro (c.3707G>C) pathogenic?

NBAS p.Arg1236Pro (c.3707G>C) is classified Uncertain significance in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely pathogenic (0.9829); Absent from gnomAD v4.1.

How common is NBAS p.Arg1236Pro (c.3707G>C) in the general population?

NBAS p.Arg1236Pro (c.3707G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NBAS p.Arg1236Pro (c.3707G>C)?

AlphaMissense predicts likely pathogenic (score 0.9829) — an in-silico prediction, not a clinical call.

NBAS p.Arg1236Pro

c.3707G>C · rs754435346 · VCV1392732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9829 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9829	likely pathogenic · top 1% in NBAS
REVEL	0.726	pathogenic-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	26.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NBAS
Protein: p.Arg1236Pro
Coding: c.3707G>C
MANE Select: NM_015909
dbSNP: rs754435346
Type: single nucleotide variant
Location: chr2:15366690 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1236: 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

Similar variants

NBAS p.Arg1236Ter Pathogenic/Likely pathogenic ★★ same residue
NBAS p.Arg1236Leu Uncertain significance ★★ ⚠ same residue
NBAS p.Arg1236= Likely benign ★ same residue
NBAS c.1726-2A>G Likely pathogenic ★★ same type
NBAS c.173-2A>G Likely pathogenic ★★ same type
NBAS c.209+2T>G Pathogenic/Likely pathogenic ★★ same type
NBAS c.2423+404G>C Likely pathogenic ★★ same type
NBAS c.335+1G>C Pathogenic/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/nbas-p-arg1236pro (accessed [today's date]).

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