Is CFH p.Cys984Arg (c.2950T>C) pathogenic?

CFH p.Cys984Arg (c.2950T>C) is classified Conflicting classifications of pathogenicity in CFH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.9773); Absent from gnomAD v4.1; Associated with age related macular degeneration 4.

What condition is associated with CFH p.Cys984Arg (c.2950T>C)?

CFH p.Cys984Arg (c.2950T>C) is associated with age related macular degeneration 4, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Cys984Arg (c.2950T>C) in the general population?

CFH p.Cys984Arg (c.2950T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFH p.Cys984Arg (c.2950T>C)?

AlphaMissense predicts likely pathogenic (score 0.9773) — an in-silico prediction, not a clinical call.

CFH p.Cys984Arg

c.2950T>C · rs886039869 · VCV265982

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9773 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,934)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

age related macular degeneration 4

Computational evidence

Protein change
AlphaMissense	0.9773	likely pathogenic · top 3% in CFH
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -16.08	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,613,934). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFH
Protein: p.Cys984Arg
Coding: c.2950T>C
MANE Select: NM_000186
dbSNP: rs886039869
Type: single nucleotide variant
Location: chr1:196740786 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 984: the sushi 16 domain; a disulfide bond

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

Disease context

Also linked: basal laminar drusen hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency atypical hemolytic-uremic syndrome

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-cys984arg (accessed [today's date]).

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