Is CFHR5 p.Pro282Leu (c.845C>T) pathogenic?

CFHR5 p.Pro282Leu (c.845C>T) is classified Likely benign in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0953); Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with CFHR5 p.Pro282Leu (c.845C>T)?

CFHR5 p.Pro282Leu (c.845C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFHR5 p.Pro282Leu (c.845C>T) in the general population?

CFHR5 p.Pro282Leu (c.845C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about CFHR5 p.Pro282Leu (c.845C>T)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

CFHR5 p.Pro282Leu

c.845C>T · VCV4227354

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -1.8
Regional constraint	o/e 1.15	unconstrained · MANE · 31 kb · p 0.00015 · regional, not allelic
Overall
CADD	0.107	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 0.0147% African / African-American · 11/74,874 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.00136% 22/1,613,676 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,807
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000678%	147,474

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: CFHR5
Protein: p.Pro282Leu
Coding: c.845C>T
MANE Select: NM_030787
Type: single nucleotide variant
Location: chr1:196996076 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 282: a disulfide bond; the sushi 5 domain

Full CFHR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFHR5 p.Pro282= Likely benign ★★ same residue
CFHR5 p.Arg132Gln Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg132Trp Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg356Cys Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg364Ser Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn126His Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn230Asp Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asp24Ala 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/cfhr5-p-pro282leu (accessed [today's date]).

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