Is CFH p.Cys192Phe (c.575G>T) pathogenic?

CFH p.Cys192Phe (c.575G>T) is classified Likely pathogenic in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.9734); Absent from gnomAD v4.1; Associated with age related macular degeneration 4.

What condition is associated with CFH p.Cys192Phe (c.575G>T)?

CFH p.Cys192Phe (c.575G>T) is associated with age related macular degeneration 4 (ClinVar).

How common is CFH p.Cys192Phe (c.575G>T) in the general population?

CFH p.Cys192Phe (c.575G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFH p.Cys192Phe (c.575G>T)?

AlphaMissense predicts likely pathogenic (score 0.9734) — an in-silico prediction, not a clinical call.

CFH p.Cys192Phe

c.575G>T · VCV4291300

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9734 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 4

Computational evidence

Protein change
AlphaMissense	0.9734	likely pathogenic ✓ concordant with ClinVar · top 4% in CFH
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -15.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.84 · regional, not allelic
Overall
CADD	25.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFH
Protein: p.Cys192Phe
Coding: c.575G>T
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196677623 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 192: a β-strand; a disulfide bond; the sushi 3 domain

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

Disease context

age related macular degeneration 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFH p.Cys192Trp Uncertain significance ★ ⚠ same residue
CFH p.Cys192Tyr Uncertain significance ★ ⚠ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg53Cys Pathogenic/Likely pathogenic ★★ same condition
CFH p.Cys431Ser Likely pathogenic ★★ same condition
CFH p.Cys611Ter 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-cys192phe (accessed [today's date]).

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