Is CFI p.Arg201Ser (c.603A>C) pathogenic?

CFI p.Arg201Ser (c.603A>C) is classified Benign/Likely benign in CFI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1959); Low-frequency (popmax 1.37%, eas); Associated with atypical hemolytic-uremic syndrome with I factor anomaly.

What condition is associated with CFI p.Arg201Ser (c.603A>C)?

CFI p.Arg201Ser (c.603A>C) is associated with atypical hemolytic-uremic syndrome with I factor anomaly, complement factor I deficiency, age related macular degeneration 13 (ClinVar).

How common is CFI p.Arg201Ser (c.603A>C) in the general population?

CFI p.Arg201Ser (c.603A>C) is low-frequency (popmax 1.37%, eas) (gnomAD).

What do computational predictors say about CFI p.Arg201Ser (c.603A>C)?

AlphaMissense predicts likely benign (score 0.1959) — an in-silico prediction, not a clinical call.

CFI p.Arg201Ser

c.603A>C · rs145769028 · VCV902337

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1959 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome with I factor anomaly

Computational evidence

Protein change
AlphaMissense	0.1959	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.10	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 -0.3	GERP -0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	15.49	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 1.37% East Asian · 613/44,868 alleles

Filtering AF 1.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.24%

Overall 0.0383% 618/1,614,168 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.37%	73
Remaining individualsnot grpmax-eligible	0.008%	12,502

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: CFI
Protein: p.Arg201Ser
Coding: c.603A>C
MANE Select: NM_000204
dbSNP: rs145769028
Type: single nucleotide variant
Location: chr4:109761572 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 201: a disulfide bond; the srcr domain

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

Disease context

atypical hemolytic-uremic syndrome with I factor anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: complement factor I deficiency age related macular degeneration 13

Similar variants

CFI p.Arg201Gly Uncertain significance ★★ ⚠ same residue
CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same condition
CFI c.57+1G>C Likely pathogenic ★★ same condition
CFI c.658+1G>A Likely pathogenic ★★ same condition
CFI c.905-1G>C Likely pathogenic ★★ same condition
CFI p.Ala258Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ same condition
CFI p.Arg474Ter Pathogenic/Likely pathogenic ★★ 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/cfi-p-arg201ser (accessed [today's date]).

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