Is CFHR1 p.Ile70Val (c.208A>G) pathogenic?

CFHR1 p.Ile70Val (c.208A>G) is classified Uncertain significance in CFHR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-01). AlphaMissense: likely benign (0.1746); Very rare (popmax 0.00342%, afr); Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFHR1 p.Ile70Val (c.208A>G)?

CFHR1 p.Ile70Val (c.208A>G) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFHR1 p.Ile70Val (c.208A>G) in the general population?

CFHR1 p.Ile70Val (c.208A>G) is very rare (popmax 0.00342%, afr) (gnomAD).

What do computational predictors say about CFHR1 p.Ile70Val (c.208A>G)?

AlphaMissense predicts likely benign (score 0.1746) — an in-silico prediction, not a clinical call.

CFHR1 p.Ile70Val

c.208A>G · rs1455233012 · VCV2395414

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00342%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.1746	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.88	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 0.61	GERP 1.8
Regional constraint	o/e 0.74	unconstrained · MANE · 8,251 bp · p 0.0011 · regional, not allelic
Overall
CADD	14.28	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 0.00342% African / African-American · 2/58,452 alleles

Filtering AF 0.000568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000327%

Overall 0.000852% 13/1,525,150 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00342%	29,226
Remaining individualsnot grpmax-eligible	0.0017%	58,916
European (non-Finnish)	0.000886%	112,917

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.Ile70Val
Coding: c.208A>G
MANE Select: NM_002113
dbSNP: rs1455233012
Type: single nucleotide variant
Location: chr1:196825626 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB
Residue 70: a disulfide bond; the sushi 1 domain; a β-strand

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.Gln44Ter Uncertain significance ★★ same condition
CFHR1 p.Ile214Asn 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
CFHR1 p.Leu290Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CFHR1 p.Asp35fs Uncertain significance ★ same condition
CFHR1 p.Ser6_Val7insTer Conflicting classifications of pathogenicity ★ 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-ile70val (accessed [today's date]).

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