Is CFHR5 p.Val130= (c.390A>G) pathogenic?

CFHR5 p.Val130= (c.390A>G) is classified Likely benign in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Ultra-rare (popmax 0.0383%, amr).

How common is CFHR5 p.Val130= (c.390A>G) in the general population?

CFHR5 p.Val130= (c.390A>G) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

CFHR5 p.Val130=

c.390A>G · rs752687157 · VCV2146011

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

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 -3.2	GERP -1.1
Overall
CADD	0.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0383% Admixed American · 23/59,986 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00149% 24/1,613,752 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,608
African / African-American	0.00133%	74,916

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.Val130=
Coding: c.390A>G
MANE Select: NM_030787
dbSNP: rs752687157
Type: single nucleotide variant
Location: chr1:196984097 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 130: a disulfide bond; the sushi 2 domain

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

Similar variants

CFHR5 p.Val130Ile Uncertain significance ★ ⚠ same residue
CFHR5 c.430+5G>T Uncertain significance ★★ same type
CFHR5 c.607+4A>G Uncertain significance ★★ same type
CFHR5 c.608-3T>A Uncertain significance ★★ same type
CFHR5 p.Arg132Gln Uncertain significance ★★ ⚠ same type
CFHR5 p.Arg132Trp Uncertain significance ★★ ⚠ same type
CFHR5 p.Arg354Gly Uncertain significance ★★ ⚠ same type
CFHR5 p.Arg356Cys Uncertain significance ★★ ⚠ 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/cfhr5-p-val130 (accessed [today's date]).

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