Is NBAS p.Val2177Phe (c.6529G>T) pathogenic?

NBAS p.Val2177Phe (c.6529G>T) is classified Conflicting classifications of pathogenicity in NBAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-22). AlphaMissense: likely benign (0.1416); Ultra-rare (popmax 0.0825%, mid); Associated with Inborn genetic diseases.

What condition is associated with NBAS p.Val2177Phe (c.6529G>T)?

NBAS p.Val2177Phe (c.6529G>T) is associated with Inborn genetic diseases (ClinVar).

How common is NBAS p.Val2177Phe (c.6529G>T) in the general population?

NBAS p.Val2177Phe (c.6529G>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about NBAS p.Val2177Phe (c.6529G>T)?

AlphaMissense predicts likely benign (score 0.1416) — an in-silico prediction, not a clinical call.

NBAS p.Val2177Phe

c.6529G>T · rs758372631 · VCV1389599

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1416 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1416	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -8.12	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 -0.48	GERP -4.2
Regional constraint	o/e 1.03	unconstrained · MANE · 394 kb · p 0.09 · regional, not allelic
Overall
CADD	5.145	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 0.0825% Middle Eastern · 5/6,060 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00489% 79/1,613,944 alleles · ultra-rare exomes 75/1,461,702 · genomes 4/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Admixed American	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.00398%	25,105
Finnishnot grpmax-eligible	0.00156%	64,008
African / African-American	0.00133%	75,010

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.Val2177Phe
Coding: c.6529G>T
MANE Select: NM_015909
dbSNP: rs758372631
Type: single nucleotide variant
Location: chr2:15190307 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.42
Residue 2177: 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

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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-val2177phe (accessed [today's date]).

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