Is CFHR3 p.Phe34Cys (c.101T>G) pathogenic?

CFHR3 p.Phe34Cys (c.101T>G) is classified Benign/Likely benign in CFHR3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-12-04). AlphaMissense: likely pathogenic (0.6398); Low-frequency (popmax 3.35%, afr); Associated with kidney disorder.

What condition is associated with CFHR3 p.Phe34Cys (c.101T>G)?

CFHR3 p.Phe34Cys (c.101T>G) is associated with kidney disorder, hemolytic uremic syndrome, atypical, susceptibility to, 1, age related macular degeneration 1 (ClinVar).

How common is CFHR3 p.Phe34Cys (c.101T>G) in the general population?

CFHR3 p.Phe34Cys (c.101T>G) is low-frequency (popmax 3.35%, afr) (gnomAD).

What do computational predictors say about CFHR3 p.Phe34Cys (c.101T>G)?

AlphaMissense predicts likely pathogenic (score 0.6398) — an in-silico prediction, not a clinical call.

CFHR3 p.Phe34Cys

c.101T>G · rs61737523 · VCV730391

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6398 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.35%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

kidney disorder

Computational evidence

Protein change
AlphaMissense	0.6398	likely pathogenic
REVEL	0.2	benign-leaning
SaProt	LLR -9.05	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.073	GERP -3.4
Regional constraint	o/e 0.72	unconstrained · MANE · 15 kb · p 1.1e-05 · regional, not allelic
Overall
CADD	15.37	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 3.35% African / African-American · 2,032/60,698 alleles

Filtering AF 3.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.18%

Overall 0.149% 2,279/1,530,158 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.35%	30
Remaining individualsnot grpmax-eligible	0.21%	477
Middle Eastern	0.205%	487
Admixed American	0.129%	777
South Asian	0.0112%	8,956
European (non-Finnish)	0.00248%	40,372

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: CFHR3
Protein: p.Phe34Cys
Coding: c.101T>G
MANE Select: NM_021023
dbSNP: rs61737523
Type: single nucleotide variant
Location: chr1:196779204 (GRCh38)
Gene constraint: LOEUF 1.302 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.93
Residue 34: a disulfide bond; the sushi 1 domain

Full CFHR3 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

Also linked: hemolytic uremic syndrome, atypical, susceptibility to, 1 age related macular degeneration 1

Similar variants

CFHR3 p.Phe34fs Uncertain significance ★ same residue
CFHR3 p.Phe34Leu Uncertain significance ★ ⚠ same residue
CFHR3 p.Arg142Cys Benign ★★ ⚠ same condition
CFHR3 p.Cys268Phe Likely benign ★★ same condition
CFHR3 p.Gln240His Benign ★★ ⚠ same condition
CFHR3 p.Ile269Val Likely benign ★★ same condition
CFHR3 p.Ile312Phe Benign/Likely benign ★★ same condition
CFHR3 p.Gly119Arg Uncertain significance ★ ⚠ 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/cfhr3-p-phe34cys (accessed [today's date]).

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