Is CFB p.Arg605Ter (c.1813C>T) pathogenic?

CFB p.Arg605Ter (c.1813C>T) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-16). Very rare (popmax 0.00223%, eas).

How common is CFB p.Arg605Ter (c.1813C>T) in the general population?

CFB p.Arg605Ter (c.1813C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CFB p.Arg605Ter

c.1813C>T · rs754972855 · VCV3006699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,612,866 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000169%	590,009

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.Arg605Ter
Coding: c.1813C>T
MANE Select: NM_001710
dbSNP: rs754972855
Type: single nucleotide variant
Location: chr6:31950902 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 605: an α-helix; a disulfide bond; the peptidase s1 domain

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

Similar variants

CFB p.Arg605Gln 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
CFB p.Arg138Gln 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-arg605ter (accessed [today's date]).

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