Is CFHR1 p.Asn149= (c.447T>C) pathogenic?

CFHR1 p.Asn149= (c.447T>C) is classified Benign in CFHR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-03-10). Common (popmax 8.59%, afr) — too common for a highly-penetrant pathogenic allele; Associated with kidney disorder.

What condition is associated with CFHR1 p.Asn149= (c.447T>C)?

CFHR1 p.Asn149= (c.447T>C) is associated with kidney disorder (ClinVar).

CFHR1 p.Asn149=

Q: How common is CFHR1 p.Asn149= (c.447T>C) in the general population?

CFHR1 p.Asn149= (c.447T>C) is common (popmax 8.59%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.447T>C · rs111236855 · VCV1229176

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 8.59%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

kidney disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -0.93
Overall
CADD	3.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.59% African / African-American · 4,258/49,554 alleles

Filtering AF 8.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.29%

Overall 0.336% 4,970/1,480,082 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.59%	12
Remaining individualsnot grpmax-eligible	0.462%	217
Middle Eastern	0.407%	245
Admixed American	0.38%	263
South Asian	0.0475%	2,106
European (non-Finnish)	0.0165%	6,043

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: CFHR1
Protein: p.Asn149=
Coding: c.447T>C
MANE Select: NM_002113
dbSNP: rs111236855
Type: single nucleotide variant
Location: chr1:196828086 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.21 · 2 PDB
Residue 149: a disulfide bond; the sushi 3 domain

Full CFHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFHR1 p.Asp218Asn Uncertain significance ★★ ⚠ same type
CFHR1 p.Gln44Ter Uncertain significance ★★ same type
CFHR1 p.Ile214Asn Uncertain significance ★★ ⚠ same type
CFHR1 p.Ile70Val Uncertain significance ★★ ⚠ same type
CFHR1 p.Pro223Leu Uncertain significance ★★ ⚠ same type
CFHR1 p.Tyr304Cys Uncertain significance ★★ ⚠ same type
CFHR1 c.253+108G>C Benign ★★ same type
CFHR1 c.253+213G>A Benign ★★ same type

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/cfhr1-p-asn149 (accessed [today's date]).

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