Is CFHR5 p.Lys162= (c.486A>G) pathogenic?

CFHR5 p.Lys162= (c.486A>G) is classified Benign/Likely benign in CFHR5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.711%, afr).

How common is CFHR5 p.Lys162= (c.486A>G) in the general population?

CFHR5 p.Lys162= (c.486A>G) is rare (popmax 0.711%, afr) (gnomAD).

CFHR5 p.Lys162=

c.486A>G · rs77344042 · VCV2056269

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.711%, afr)

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 0.064	GERP -0.94
Overall
CADD	0.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.711% African / African-American · 533/74,994 alleles

Filtering AF 0.661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.641%

Overall 0.0386% 623/1,613,690 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.711%	141
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Middle Eastern	0.0331%	3,025
Admixed American	0.0317%	3,159
South Asian	0.00659%	15,175
European (non-Finnish)	0.00356%	28,090

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.Lys162=
Coding: c.486A>G
MANE Select: NM_030787
dbSNP: rs77344042
Type: single nucleotide variant
Location: chr1:196994135 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 162: a disulfide bond; the sushi 3 domain

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

Similar variants

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
CFHR5 p.Arg364Ser 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-lys162 (accessed [today's date]).

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