Is CFB p.Ile502Thr (c.1505T>C) pathogenic?

CFB p.Ile502Thr (c.1505T>C) is classified Conflicting classifications of pathogenicity in CFB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-09-17). AlphaMissense: likely benign (0.0543); Ultra-rare (popmax 0.0121%, sas); Associated with Inborn genetic diseases.

What condition is associated with CFB p.Ile502Thr (c.1505T>C)?

CFB p.Ile502Thr (c.1505T>C) is associated with Inborn genetic diseases, atypical hemolytic-uremic syndrome (ClinVar).

How common is CFB p.Ile502Thr (c.1505T>C) in the general population?

CFB p.Ile502Thr (c.1505T>C) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about CFB p.Ile502Thr (c.1505T>C)?

AlphaMissense predicts likely benign (score 0.0543) — an in-silico prediction, not a clinical call.

CFB p.Ile502Thr

c.1505T>C · VCV3491515

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0543	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -3.11	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 0.26	GERP -1.6, phastCons 0.29
Overall
CADD	7.858	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 0.0121% South Asian · 11/91,086 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00205% 30/1,460,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,281
Remaining individualsnot grpmax-eligible	0.0064%	15,624
East Asian	0.00223%	44,876
Admixed American	0.00167%	60,014
Finnishnot grpmax-eligible	0.00159%	62,906
European (non-Finnish)	0.00102%	98,333

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.Ile502Thr
Coding: c.1505T>C
MANE Select: NM_001710
Type: single nucleotide variant
Location: chr6:31950146 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 502: a disulfide bond; the peptidase s1 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

Also linked: atypical hemolytic-uremic syndrome

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.Arg138Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg138Trp Uncertain significance ★★ ⚠ same condition
CFB p.Arg193Gln Uncertain significance ★★ ⚠ same condition
CFB p.Arg203Gln 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-ile502thr (accessed [today's date]).

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