Is CFB p.Ile101Val (c.301A>G) pathogenic?

CFB p.Ile101Val (c.301A>G) is classified Uncertain significance in CFB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-09). AlphaMissense: likely benign (0.0778); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Ile101Val (c.301A>G)?

CFB p.Ile101Val (c.301A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFB p.Ile101Val (c.301A>G) in the general population?

CFB p.Ile101Val (c.301A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CFB p.Ile101Val (c.301A>G)?

AlphaMissense predicts likely benign (score 0.0778) — an in-silico prediction, not a clinical call.

CFB p.Ile101Val

c.301A>G · rs980506964 · VCV1007177

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0778 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0778	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.98	acceptor gain · deltas
Pangolin	Δ0.72	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.1	GERP 1.5, phastCons 1
Overall
CADD	23.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000958% 14/1,460,768 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0192%	5,208
East Asiangrpmax	0.00446%	22,427

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFB
Protein: p.Ile101Val
Coding: c.301A>G
MANE Select: NM_001710
dbSNP: rs980506964
Type: single nucleotide variant
Location: chr6:31947009 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 101: the sushi 2 domain

Full CFB 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

Similar variants

CFB p.Ala162Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala289Val Uncertain significance ★★ ⚠ same condition
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same condition
CFB p.Arg117Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg193Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg419Lys Uncertain significance ★★ ⚠ same condition
CFB p.Arg642Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg730Trp Uncertain significance ★★ ⚠ 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/cfb-p-ile101val (accessed [today's date]).

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