Is FBF1 p.Lys975Arg (c.2924A>G) pathogenic?

FBF1 p.Lys975Arg (c.2924A>G) is classified Uncertain significance in FBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.1294); Very rare (popmax 0.00175%, amr).

How common is FBF1 p.Lys975Arg (c.2924A>G) in the general population?

FBF1 p.Lys975Arg (c.2924A>G) is very rare (popmax 0.00175%, amr) (gnomAD).

What do computational predictors say about FBF1 p.Lys975Arg (c.2924A>G)?

AlphaMissense predicts likely benign (score 0.1294) — an in-silico prediction, not a clinical call.

FBF1 p.Lys975Arg

c.2924A>G · rs2065473795 · VCV2234277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1294 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1294	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -5.23	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 5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K960R vs ClinVar K975R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% Admixed American · 1/57,030 alleles

Overall 6.28e-05% 1/1,593,488 alleles · very rare exomes 1/1,441,176 · genomes 0/152,312 · joint denominator

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.Lys975Arg
Coding: c.2924A>G
MANE Select: NM_001319193
dbSNP: rs2065473795
Type: single nucleotide variant
Location: chr17:75914189 (GRCh38)
Gene constraint: LOEUF 1.133 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.11
Residue 960 UniProt numbering: a cross-link site

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-lys975arg (accessed [today's date]).

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