Is CFHR1 p.Asp35fs (c.104del) pathogenic?

CFHR1 p.Asp35fs (c.104del) is classified Uncertain significance in CFHR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). Rare (popmax 0.343%, eas); Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFHR1 p.Asp35fs (c.104del)?

CFHR1 p.Asp35fs (c.104del) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFHR1 p.Asp35fs (c.104del) in the general population?

CFHR1 p.Asp35fs (c.104del) is rare (popmax 0.343%, eas) (gnomAD).

CFHR1 p.Asp35fs

c.104del · VCV3779513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.343%, eas)

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.16	GERP -1.7
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.343% East Asian · 153/44,552 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.282%

Overall 0.0102% 155/1,519,322 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.343%	291
Remaining individualsnot grpmax-eligible	0.00341%	29,356

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: CFHR1
Protein: p.Asp35fs
Coding: c.104del
MANE Select: NM_002113
Type: Deletion
Location: chr1:196825522 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB
Residue 35: the sushi 1 domain; a disulfide bond

Full CFHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hemolytic uremic syndrome, atypical, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFHR1 p.Asp35= Benign/Likely benign ★★ same residue
CFHR1 p.Ser6_Val7insTer Conflicting classifications of pathogenicity ★ same condition
CFHR1 p.Gln44Ter Uncertain significance ★★ same condition
CFHR1 p.Ile214Asn Uncertain significance ★★ ⚠ same condition
CFHR1 p.Ile70Val Uncertain significance ★★ ⚠ same condition
CFHR1 p.Asp215Asn Uncertain significance ★ ⚠ same condition
CFHR1 p.Cys208Tyr Uncertain significance ★ same condition
CFHR1 p.Glu258Asp 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/cfhr1-p-asp35fs (accessed [today's date]).

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