Is CFH p.Thr95= (c.285T>C) pathogenic?

CFH p.Thr95= (c.285T>C) is classified Conflicting classifications of pathogenicity in CFH (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0556%, nfe); Associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II.

What condition is associated with CFH p.Thr95= (c.285T>C)?

CFH p.Thr95= (c.285T>C) is associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Thr95= (c.285T>C) in the general population?

CFH p.Thr95= (c.285T>C) is ultra-rare (popmax 0.0556%, nfe) (gnomAD).

CFH p.Thr95=

c.285T>C · rs148182625 · VCV294482

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0556%, nfe)

Conditions

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -3.4, phastCons 0.001
Overall
CADD	3.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0556% European (non-Finnish) · 656/1,179,724 alleles

Filtering AF 0.052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.0484% 781/1,613,506 alleles · ultra-rare exomes 709/1,461,374 · genomes 72/152,132 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.26%	384
European (non-Finnish)grpmax	0.0556%	1,798
Remaining individualsnot grpmax-eligible	0.0464%	2,154
Admixed American	0.015%	6,666
African / African-American	0.0107%	9,361
East Asian	0.00223%	44,772
Finnishnot grpmax-eligible	0.00156%	64,020

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr95=
Coding: c.285T>C
MANE Select: NM_000186
dbSNP: rs148182625
Type: single nucleotide variant
Location: chr1:196673897 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 95: a β-strand; the sushi 2 domain

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 age related macular degeneration 4

Similar variants

CFH p.Thr95Asn Uncertain significance ★ ⚠ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C 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.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg53Cys 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-thr95 (accessed [today's date]).

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