Is CFH p.His577Arg (c.1730A>G) pathogenic?

CFH p.His577Arg (c.1730A>G) is classified Uncertain significance in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely benign (0.0876); Very rare (popmax 0.00893%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFH p.His577Arg (c.1730A>G)?

CFH p.His577Arg (c.1730A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFH p.His577Arg (c.1730A>G) in the general population?

CFH p.His577Arg (c.1730A>G) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about CFH p.His577Arg (c.1730A>G)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

CFH p.His577Arg

c.1730A>G · VCV3266584

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -5.99	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 0.015	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	1.345	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 0.00893% East Asian · 4/44,796 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000744% 12/1,613,704 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,199
African / African-American	0.008%	12,504
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	8.48e-05%	1,179,768

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.His577Arg
Coding: c.1730A>G
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196725154 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 577: the sushi 10 domain; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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CFH p.Asn660His Uncertain significance ★★ ⚠ same condition
CFH p.Asn75His Uncertain significance ★★ ⚠ same condition
CFH p.Asp276Glu Uncertain significance ★★ ⚠ same condition
CFH p.Asp855Asn Uncertain significance ★★ ⚠ same condition
CFH p.Asp947His 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/cfh-p-his577arg (accessed [today's date]).

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