Is CFHR5 p.Pro41Arg (c.122C>G) pathogenic?

CFHR5 p.Pro41Arg (c.122C>G) is classified Likely benign in CFHR5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-28). AlphaMissense: likely benign (0.0731); Ultra-rare (popmax 0.0999%, sas); Associated with Inborn genetic diseases.

What condition is associated with CFHR5 p.Pro41Arg (c.122C>G)?

CFHR5 p.Pro41Arg (c.122C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFHR5 p.Pro41Arg (c.122C>G) in the general population?

CFHR5 p.Pro41Arg (c.122C>G) is ultra-rare (popmax 0.0999%, sas) (gnomAD).

What do computational predictors say about CFHR5 p.Pro41Arg (c.122C>G)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

CFHR5 p.Pro41Arg

c.122C>G · rs762367817 · VCV2161762

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -4.10	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 -2.8	GERP -3.7
Regional constraint	o/e 1.15	unconstrained · MANE · 31 kb · p 0.00015 · regional, not allelic
Overall
CADD	1.723	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 0.0999% South Asian · 91/91,050 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0771%

Overall 0.00576% 93/1,613,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Pro41Arg
Coding: c.122C>G
MANE Select: NM_030787
dbSNP: rs762367817
Type: single nucleotide variant
Location: chr1:196982948 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 41: 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.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
CFHR5 p.Asp535Gly 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-pro41arg (accessed [today's date]).

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