Is FBF1 p.Ile80Val (c.238A>G) pathogenic?

FBF1 p.Ile80Val (c.238A>G) is classified Likely benign in FBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.0885); Ultra-rare (popmax 0.023%, mid).

How common is FBF1 p.Ile80Val (c.238A>G) in the general population?

FBF1 p.Ile80Val (c.238A>G) is ultra-rare (popmax 0.023%, mid) (gnomAD).

What do computational predictors say about FBF1 p.Ile80Val (c.238A>G)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

FBF1 p.Ile80Val

c.238A>G · rs766190975 · VCV2255948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.73	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 -7.4	GERP -2.5
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	0.023	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 I66V vs ClinVar I80V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,356 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000619%

Overall 0.00132% 20/1,520,192 alleles · ultra-rare exomes 15/1,378,608 · genomes 5/141,584 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,356
African / African-American	0.00433%	23,095
Admixed American	0.00202%	49,570
Remaining individualsnot grpmax-eligible	0.00172%	57,994
South Asian	0.00119%	84,166
European (non-Finnish)	0.00115%	87,066

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.Ile80Val
Coding: c.238A>G
MANE Select: NM_001319193
dbSNP: rs766190975
Type: single nucleotide variant
Location: chr17:75930038 (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.Asp80Val Uncertain significance ★ same residue
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

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-ile80val (accessed [today's date]).

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