Is CFI p.Ser570Thr (c.1709G>C) pathogenic?

CFI p.Ser570Thr (c.1709G>C) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-09-17). AlphaMissense: likely benign (0.221); Ultra-rare (popmax 0.0209%, nfe); Associated with complement factor I deficiency.

What condition is associated with CFI p.Ser570Thr (c.1709G>C)?

CFI p.Ser570Thr (c.1709G>C) is associated with complement factor I deficiency, atypical hemolytic-uremic syndrome with I factor anomaly, age related macular degeneration 13 (ClinVar).

How common is CFI p.Ser570Thr (c.1709G>C) in the general population?

CFI p.Ser570Thr (c.1709G>C) is ultra-rare (popmax 0.0209%, nfe) (gnomAD).

How is Immunodeficiency with factor I anomaly inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CFI p.Ser570Thr (c.1709G>C)?

AlphaMissense predicts likely benign (score 0.221) — an in-silico prediction, not a clinical call.

CFI p.Ser570Thr

c.1709G>C · rs200973120 · VCV438686

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.221 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

complement factor I deficiency

Computational evidence

Protein change
AlphaMissense	0.221	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.51, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% European (non-Finnish) · 247/1,180,010 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.0156% 251/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0209%	4,777
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,000
African / African-American	0.00133%	74,910

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.Ser570Thr
Coding: c.1709G>C
MANE Select: NM_000204
dbSNP: rs200973120
Type: single nucleotide variant
Location: chr4:109740936 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 570: an α-helix; the peptidase s1 domain

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

Disease context

complement factor I deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with I factor anomaly age related macular degeneration 13 atypical hemolytic-uremic syndrome

For Immunodeficiency with factor I anomaly (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

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
CFI c.773-3C>T 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/cfi-p-ser570thr (accessed [today's date]).

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