Is CFH p.His980= (c.2940C>T) pathogenic?

CFH p.His980= (c.2940C>T) is classified Likely benign in CFH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). Rare (popmax 0.6%, eas); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFH p.His980= (c.2940C>T)?

CFH p.His980= (c.2940C>T) is associated with atypical hemolytic-uremic syndrome (ClinVar).

How common is CFH p.His980= (c.2940C>T) in the general population?

CFH p.His980= (c.2940C>T) is rare (popmax 0.6%, eas) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

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

CFH p.His980=

c.2940C>T · rs79934209 · VCV1903029

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.6%, eas)

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.7
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.6% East Asian · 269/44,828 alleles

Filtering AF 0.541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.518%

Overall 0.0168% 271/1,613,800 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.6%	167
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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: CFH
Protein: p.His980=
Coding: c.2940C>T
MANE Select: NM_000186
dbSNP: rs79934209
Type: single nucleotide variant
Location: chr1:196740776 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 980: the sushi 16 domain; a disulfide bond

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

Disease context

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

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Leu Likely pathogenic ★★ ⚠ same condition
CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg53Cys Pathogenic/Likely pathogenic ★★ same condition
CFH p.Cys569Ter 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/cfh-p-his980 (accessed [today's date]).

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