Is NBAS p.Phe1729Val (c.5185T>G) pathogenic?

NBAS p.Phe1729Val (c.5185T>G) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1429); Ultra-rare (popmax 0.0684%, amr).

How common is NBAS p.Phe1729Val (c.5185T>G) in the general population?

NBAS p.Phe1729Val (c.5185T>G) is ultra-rare (popmax 0.0684%, amr) (gnomAD).

What do computational predictors say about NBAS p.Phe1729Val (c.5185T>G)?

AlphaMissense predicts likely benign (score 0.1429) — an in-silico prediction, not a clinical call.

NBAS p.Phe1729Val

c.5185T>G · rs778307927 · VCV1426798

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1429 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1429	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -4.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.41, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	21.7	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 0.0684% Admixed American · 41/59,948 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.046%

Overall 0.00297% 48/1,613,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0684%	1,462
Remaining individualsnot grpmax-eligible	0.0032%	31,234
European (non-Finnish)	0.000424%	235,982

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.Phe1729Val
Coding: c.5185T>G
MANE Select: NM_015909
dbSNP: rs778307927
Type: single nucleotide variant
Location: chr2:15277055 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 1729: 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 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
NBAS c.4461+2T>C Likely pathogenic ★★ same type
NBAS c.4583-2A>G Likely pathogenic ★★ same type
NBAS c.513+2T>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-phe1729val (accessed [today's date]).

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