Is CFHR5 p.Pro81Leu (c.242C>T) pathogenic?

CFHR5 p.Pro81Leu (c.242C>T) is classified Conflicting classifications of pathogenicity in CFHR5 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-03). AlphaMissense: ambiguous (0.4954); Rare (popmax 0.111%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFHR5 p.Pro81Leu (c.242C>T)?

CFHR5 p.Pro81Leu (c.242C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CFHR5 p.Pro81Leu (c.242C>T) in the general population?

CFHR5 p.Pro81Leu (c.242C>T) is rare (popmax 0.111%, eas) (gnomAD).

What do computational predictors say about CFHR5 p.Pro81Leu (c.242C>T)?

AlphaMissense predicts ambiguous (score 0.4954) — an in-silico prediction, not a clinical call.

CFHR5 p.Pro81Leu

c.242C>T · rs544857720 · VCV1331463

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4954 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4954	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -10.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -1.2
Regional constraint	o/e 1.15	unconstrained · MANE · 31 kb · p 0.00015 · regional, not allelic
Overall
CADD	19.81	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 0.111% East Asian · 50/44,848 alleles

Filtering AF 0.0868% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0781%

Overall 0.00502% 81/1,613,930 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.111%	897
Remaining individualsnot grpmax-eligible	0.0096%	10,416
European (non-Finnish)	0.00203%	49,167
South Asian	0.0011%	90,998

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.Pro81Leu
Coding: c.242C>T
MANE Select: NM_030787
dbSNP: rs544857720
Type: single nucleotide variant
Location: chr1:196983068 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 81: a disulfide bond; the sushi 1 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.Pro81= Benign/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-pro81leu (accessed [today's date]).

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