Is FBF1 p.Ala465Val (c.1394C>T) pathogenic?

FBF1 p.Ala465Val (c.1394C>T) is classified Likely benign in FBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0728); Ultra-rare (popmax 0.0536%, nfe).

How common is FBF1 p.Ala465Val (c.1394C>T) in the general population?

FBF1 p.Ala465Val (c.1394C>T) is ultra-rare (popmax 0.0536%, nfe) (gnomAD).

What do computational predictors say about FBF1 p.Ala465Val (c.1394C>T)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

FBF1 p.Ala465Val

c.1394C>T · rs201756878 · VCV2410295

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0536%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -7.74	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 -1.1	GERP -2.7
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A451V vs ClinVar A465V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0536% European (non-Finnish) · 627/1,169,056 alleles

Filtering AF 0.0501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.0424% 674/1,590,368 alleles · ultra-rare exomes 631/1,438,028 · genomes 43/152,340 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0536%	1,865
Remaining individualsnot grpmax-eligible	0.026%	3,850
African / African-American	0.0228%	4,388
Middle Eastern	0.0171%	5,852
Finnishnot grpmax-eligible	0.0114%	8,778
East Asian	0.00685%	14,606
Admixed American	0.00531%	18,833

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: FBF1
Protein: p.Ala465Val
Coding: c.1394C>T
MANE Select: NM_001319193
dbSNP: rs201756878
Type: single nucleotide variant
Location: chr17:75923216 (GRCh38)
Gene constraint: LOEUF 1.133 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.11
Residue 451 UniProt numbering: the 'disordered' region

Full FBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALB p.Arg138Ter Pathogenic ★★ same type
ALB p.Ala324Pro Uncertain significance ★★ ⚠ same type
ALB p.Ala387Ser Uncertain significance ★★ ⚠ same type
ALB p.Ala83Gly Uncertain significance ★★ ⚠ same type
ALB p.Arg105His Uncertain significance ★★ ⚠ same type
ALB p.Arg23Cys Uncertain significance ★★ ⚠ same type
ALB p.Asp197Tyr Uncertain significance ★★ ⚠ same type
ALB p.Asp37Asn Uncertain significance ★★ ⚠ 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/fbf1-p-ala465val (accessed [today's date]).

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