Is CFB p.Ile281Thr (c.842T>C) pathogenic?

CFB p.Ile281Thr (c.842T>C) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.2711); Very rare (popmax 0.00329%, sas).

How common is CFB p.Ile281Thr (c.842T>C) in the general population?

CFB p.Ile281Thr (c.842T>C) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CFB p.Ile281Thr (c.842T>C)?

AlphaMissense predicts likely benign (score 0.2711) — an in-silico prediction, not a clinical call.

CFB p.Ile281Thr

c.842T>C · rs745324553 · VCV1482867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2711	likely benign
REVEL	0.675	pathogenic-leaning
SaProt	LLR -10.27	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Overall
CADD	26.0	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.0013% 21/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Finnishnot grpmax-eligible	0.00312%	32,018
African / African-American	0.00134%	74,904
European (non-Finnish)	0.0011%	90,771

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.Ile281Thr
Coding: c.842T>C
MANE Select: NM_001710
dbSNP: rs745324553
Type: single nucleotide variant
Location: chr6:31948026 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 281: a turn; the vwfa 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-ile281thr (accessed [today's date]).

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