Is FUS p.Ala16Val (c.47C>T) pathogenic?

FUS p.Ala16Val (c.47C>T) is classified Likely benign in FUS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-17). AlphaMissense: likely benign (0.2571); Rare (popmax 0.133%, afr); Associated with Inborn genetic diseases.

What condition is associated with FUS p.Ala16Val (c.47C>T)?

FUS p.Ala16Val (c.47C>T) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Ala16Val (c.47C>T) in the general population?

FUS p.Ala16Val (c.47C>T) is rare (popmax 0.133%, afr) (gnomAD).

What do computational predictors say about FUS p.Ala16Val (c.47C>T)?

AlphaMissense predicts likely benign (score 0.2571) — an in-silico prediction, not a clinical call.

FUS p.Ala16Val

c.47C>T · rs139980267 · VCV1530335

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2571 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2571	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -9.13	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 4.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 4,906 bp · p 0.12 · regional, not allelic
Overall
CADD	27.2	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 0.133% African / African-American · 100/75,038 alleles

Filtering AF 0.112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.00688% 111/1,614,140 alleles · rare exomes 63/1,461,872 · genomes 48/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.133%	750
Remaining individualsnot grpmax-eligible	0.0096%	10,417
Admixed American	0.00833%	12,002

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: FUS
Protein: p.Ala16Val
Coding: c.47C>T
MANE Select: NM_004960
dbSNP: rs139980267
Type: single nucleotide variant
Location: chr16:31182521 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 16: the 'disordered' region

Full FUS 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

Also linked: amyotrophic lateral sclerosis type 6 tremor, hereditary essential, 4

Similar variants

FUS p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
FUS p.Arg495Ter Pathogenic ★★ same condition
FUS p.Arg514Gly Pathogenic ★★ ⚠ same condition
FUS p.Arg521Cys Pathogenic ★★ same condition
FUS p.Arg521Gly Pathogenic ★★ same condition
FUS p.Arg521His Pathogenic ★★ ⚠ same condition
FUS p.Arg521Leu Pathogenic/Likely pathogenic ★★ same condition
FUS p.Lys510Glu Pathogenic/Likely pathogenic ★★ ⚠ 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/fus-p-ala16val (accessed [today's date]).

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