Is CFI p.Asp524Val (c.1571A>T) pathogenic?

CFI p.Asp524Val (c.1571A>T) is classified Pathogenic in CFI (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9967); Very rare (popmax 0.000169%, nfe); Associated with CFI-related disorder.

What condition is associated with CFI p.Asp524Val (c.1571A>T)?

CFI p.Asp524Val (c.1571A>T) is associated with CFI-related disorder, atypical hemolytic-uremic syndrome with I factor anomaly (ClinVar).

How common is CFI p.Asp524Val (c.1571A>T) in the general population?

CFI p.Asp524Val (c.1571A>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CFI p.Asp524Val (c.1571A>T)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

CFI p.Asp524Val

c.1571A>T · rs121964914 · VCV12122

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic ✓ concordant with ClinVar · top 1% in CFI
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -15.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	28.8	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 0.000169% European (non-Finnish) · 2/1,179,978 alleles

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

Overall 0.000124% 2/1,613,862 alleles · very rare

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.Asp524Val
Coding: c.1571A>T
MANE Select: NM_000204
dbSNP: rs121964914
Type: single nucleotide variant
Location: chr4:109741074 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 524: a disulfide bond; a UniProt-annotated variant site (in ahus3); the peptidase s1 domain

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

Disease context

Also linked: atypical hemolytic-uremic syndrome with I factor anomaly

Similar variants

CFI p.Asp524Tyr Uncertain significance ★★ ⚠ same residue
CFI p.Asp524Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same condition
CFI c.57+1G>C 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-asp524val (accessed [today's date]).

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