Is CFB p.Arg710His (c.2129G>A) pathogenic?

CFB p.Arg710His (c.2129G>A) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.6803); Very rare (popmax 0.00203%, nfe).

How common is CFB p.Arg710His (c.2129G>A) in the general population?

CFB p.Arg710His (c.2129G>A) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about CFB p.Arg710His (c.2129G>A)?

AlphaMissense predicts likely pathogenic (score 0.6803) — an in-silico prediction, not a clinical call.

CFB p.Arg710His

c.2129G>A · rs758029612 · VCV2906023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6803	likely pathogenic
REVEL	0.408	indeterminate
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,040 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	64,020
African / African-American	0.00133%	74,912
South Asian	0.0011%	91,076

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.Arg710His
Coding: c.2129G>A
MANE Select: NM_001710
dbSNP: rs758029612
Type: single nucleotide variant
Location: chr6:31951594 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 710: a β-strand; a disulfide bond; the peptidase s1 domain

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

Similar variants

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
CFB p.Arg138Gln Uncertain significance ★★ ⚠ same type
CFB p.Arg138Trp 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-arg710his (accessed [today's date]).

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