Is CFH p.His402Tyr (c.1204C>T) pathogenic?

CFH p.His402Tyr (c.1204C>T) is classified Conflicting classifications of pathogenicity in CFH (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0755); Common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with basal laminar drusen.

What condition is associated with CFH p.His402Tyr (c.1204C>T)?

CFH p.His402Tyr (c.1204C>T) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

What do computational predictors say about CFH p.His402Tyr (c.1204C>T)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

CFH p.His402Tyr

Q: How common is CFH p.His402Tyr (c.1204C>T) in the general population?

CFH p.His402Tyr (c.1204C>T) is common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1204C>T · rs1061170 · VCV294490

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

basal laminar drusen

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.086	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.001	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 94.1% East Asian · 42,102/44,740 alleles

Filtering AF 93.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 93%

Overall 63.7% 1,025,522/1,610,204 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	94.1%	1
Admixed American	80.2%	1
South Asian	69.6%	1
Ashkenazi Jewishnot grpmax-eligible	65.5%	2
Remaining individualsnot grpmax-eligible	64.4%	2
Middle Eastern	63.2%	2
African / African-American	62.9%	2
European (non-Finnish)	61.6%	2
Finnishnot grpmax-eligible	56%	2
Amishnot grpmax-eligible	51.9%	2

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.His402Tyr
Coding: c.1204C>T
MANE Select: NM_000186
dbSNP: rs1061170
Type: single nucleotide variant
Location: chr1:196690107 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 402: a turn; a disulfide bond; a UniProt-annotated variant site (associated with armd4); the sushi 7 domain

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

Disease context

basal laminar drusen — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

CFH p.His402Asp Uncertain significance ★ ⚠ same residue
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

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-his402tyr (accessed [today's date]).

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