Is CFHR5 p.Tyr565= (c.1695T>C) pathogenic?

CFHR5 p.Tyr565= (c.1695T>C) is classified Likely benign in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). Ultra-rare (popmax 0.0165%, mid).

How common is CFHR5 p.Tyr565= (c.1695T>C) in the general population?

CFHR5 p.Tyr565= (c.1695T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CFHR5 p.Tyr565=

c.1695T>C · rs1654358185 · VCV2420064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -1.8	GERP -3.6
Overall
CADD	1.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00089% 13/1,460,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.00961%	10,410
African / African-American	0.00533%	18,748
European (non-Finnish)	0.00017%	589,376

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.Tyr565=
Coding: c.1695T>C
MANE Select: NM_030787
dbSNP: rs1654358185
Type: single nucleotide variant
Location: chr1:197008668 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 565: the sushi 9 domain; a disulfide bond

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-tyr565 (accessed [today's date]).

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