Is CFH p.Val1007Leu (c.3019G>T) pathogenic?

CFH p.Val1007Leu (c.3019G>T) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1061); Common (popmax 27%, afr) — too common for a highly-penetrant pathogenic allele; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFH p.Val1007Leu (c.3019G>T)?

CFH p.Val1007Leu (c.3019G>T) is associated with atypical hemolytic-uremic syndrome, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How is Atypical hemolytic uremic syndrome inherited?

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

What do computational predictors say about CFH p.Val1007Leu (c.3019G>T)?

AlphaMissense predicts likely benign (score 0.1061) — an in-silico prediction, not a clinical call.

CFH p.Val1007Leu

Q: How common is CFH p.Val1007Leu (c.3019G>T) in the general population?

CFH p.Val1007Leu (c.3019G>T) is common (popmax 27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3019G>T · rs534399 · VCV294514

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely benign

0.1061 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 27%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.1061	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.98	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 0.24	GERP -3.7
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	1.006	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 27% African / African-American · 20,199/74,944 alleles

Filtering AF 26.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.5%

Overall 1.55% 25,084/1,614,074 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	27%	4
Ashkenazi Jewishnot grpmax-eligible	2.88%	35
Remaining individualsnot grpmax-eligible	2.3%	43
Admixed American	2.12%	47
Middle Eastern	1.82%	55
South Asian	0.168%	595
European (non-Finnish)	0.0899%	1,112

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.Val1007Leu
Coding: c.3019G>T
MANE Select: NM_000186
dbSNP: rs534399
Type: single nucleotide variant
Location: chr1:196741937 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1007: a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in); the sushi 17 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

Also linked: basal laminar drusen hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency age related macular degeneration 4

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.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.350+1G>T 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

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-val1007leu (accessed [today's date]).

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