Is CFB p.Val734Glu (c.2201T>A) pathogenic?

CFB p.Val734Glu (c.2201T>A) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely benign (0.1312); Very rare (popmax 0.004%, afr).

How common is CFB p.Val734Glu (c.2201T>A) in the general population?

CFB p.Val734Glu (c.2201T>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CFB p.Val734Glu (c.2201T>A)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

CFB p.Val734Glu

c.2201T>A · VCV3702301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -9.91	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 -0.57	GERP -4.1
Overall
CADD	13.96	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 0.004% African / African-American · 3/74,936 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,996 alleles · very rare

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.Val734Glu
Coding: c.2201T>A
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31951936 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 734: the peptidase s1 domain

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

Similar variants

CFB p.Val734Leu Uncertain significance ★ ⚠ same residue
CFB p.Val734fs Uncertain significance ★ same residue
CFB c.2140-1G>C Uncertain significance ★★ same type
CFB c.-3G>A Uncertain significance ★★ same type
CFB p.Ala162Val Uncertain significance ★★ ⚠ same type
CFB p.Ala289Val Uncertain significance ★★ same type
CFB p.Ala567Gly Uncertain significance ★★ ⚠ same type
CFB p.Arg117Trp 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/cfb-p-val734glu (accessed [today's date]).

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