Is FBF1 p.Arg618Trp (c.1852C>T) pathogenic?

FBF1 p.Arg618Trp (c.1852C>T) is classified Uncertain significance in FBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.2707); Ultra-rare (popmax 0.0148%, afr).

How common is FBF1 p.Arg618Trp (c.1852C>T) in the general population?

FBF1 p.Arg618Trp (c.1852C>T) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about FBF1 p.Arg618Trp (c.1852C>T)?

AlphaMissense predicts likely benign (score 0.2707) — an in-silico prediction, not a clinical call.

FBF1 p.Arg618Trp

c.1852C>T · rs376971539 · VCV2212613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2707	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.26, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	25.8	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 R604W vs ClinVar R618W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% African / African-American · 11/74,156 alleles

Filtering AF 0.00823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00639%

Overall 0.00139% 22/1,587,932 alleles · ultra-rare exomes 17/1,435,770 · genomes 5/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,741
South Asian	0.0068%	14,698
Remaining individualsnot grpmax-eligible	0.00488%	20,478
East Asian	0.00231%	43,208
European (non-Finnish)	8.56e-05%	1,167,946

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.Arg618Trp
Coding: c.1852C>T
MANE Select: NM_001319193
dbSNP: rs376971539
Type: single nucleotide variant
Location: chr17:75920086 (GRCh38)
Gene constraint: LOEUF 1.133 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.11

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-arg618trp (accessed [today's date]).

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