Is CFHR5 p.Tyr287Cys (c.860A>G) pathogenic?

CFHR5 p.Tyr287Cys (c.860A>G) is classified Uncertain significance in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.3977); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CFHR5 p.Tyr287Cys (c.860A>G)?

CFHR5 p.Tyr287Cys (c.860A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFHR5 p.Tyr287Cys (c.860A>G) in the general population?

CFHR5 p.Tyr287Cys (c.860A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFHR5 p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts ambiguous (score 0.3977) — an in-silico prediction, not a clinical call.

CFHR5 p.Tyr287Cys

c.860A>G · VCV4001774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3977	ambiguous
REVEL	0.289	benign-leaning
SaProt	LLR -12.92	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.56, phastCons 0.001
Regional constraint	o/e 1.15	unconstrained · MANE · 31 kb · p 0.00015 · regional, not allelic
Overall
CADD	18.74	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFHR5
Protein: p.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_030787
Type: single nucleotide variant
Location: chr1:196996091 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 287: a disulfide bond; the sushi 5 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-tyr287cys (accessed [today's date]).

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