Is NBAS p.Pro1602Ser (c.4804C>T) pathogenic?

NBAS p.Pro1602Ser (c.4804C>T) is classified Uncertain significance in NBAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.7048); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Pro1602Ser (c.4804C>T)?

NBAS p.Pro1602Ser (c.4804C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Pro1602Ser (c.4804C>T) in the general population?

NBAS p.Pro1602Ser (c.4804C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about NBAS p.Pro1602Ser (c.4804C>T)?

AlphaMissense predicts likely pathogenic (score 0.7048) — an in-silico prediction, not a clinical call.

NBAS p.Pro1602Ser

c.4804C>T · rs2528204735 · VCV3177982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7048	likely pathogenic
REVEL	0.515	indeterminate
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	26.0	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 0.000169% European (non-Finnish) · 2/1,179,992 alleles

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

Overall 0.000124% 2/1,614,072 alleles · very rare exomes 2/1,461,840 · genomes 0/152,232 · 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: NBAS
Protein: p.Pro1602Ser
Coding: c.4804C>T
MANE Select: NM_015909
dbSNP: rs2528204735
Type: single nucleotide variant
Location: chr2:15292760 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1602: 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.Pro1602His Uncertain significance ★ ⚠ 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
NBAS p.Ala2341Val 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-pro1602ser (accessed [today's date]).

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