Is CD46 p.Ser287= (c.861G>A) pathogenic?

CD46 p.Ser287= (c.861G>A) is classified Benign/Likely benign in CD46 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-24). Low-frequency (popmax 1.16%, afr); Associated with kidney disorder.

What condition is associated with CD46 p.Ser287= (c.861G>A)?

CD46 p.Ser287= (c.861G>A) is associated with kidney disorder, atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (ClinVar).

How common is CD46 p.Ser287= (c.861G>A) in the general population?

CD46 p.Ser287= (c.861G>A) is low-frequency (popmax 1.16%, afr) (gnomAD).

CD46 p.Ser287=

c.861G>A · rs17006843 · VCV791828

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.16%, afr)

Conditions

kidney disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -7.6	GERP -2.9
Overall
CADD	0.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.16% African / African-American · 867/74,930 alleles

Filtering AF 1.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 0.0636% 1,026/1,612,580 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.16%	86
Admixed American	0.113%	882
Remaining individualsnot grpmax-eligible	0.0913%	1,096
Middle Eastern	0.0661%	1,514
South Asian	0.00659%	15,171
European (non-Finnish)	0.00204%	49,117

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: CD46
Protein: p.Ser287=
Coding: c.861G>A
MANE Select: NM_172351
dbSNP: rs17006843
Type: single nucleotide variant
Location: chr1:207767783 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 7 PDB

Full CD46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atypical hemolytic-uremic syndrome with MCP/CD46 anomaly

Similar variants

CD46 p.Ser287Leu Uncertain significance ★★ ⚠ same residue
CD46 c.1082+2T>A Pathogenic ★★ same condition
CD46 c.286+2T>G Pathogenic/Likely pathogenic ★★ same condition
CD46 c.287-2A>G Pathogenic/Likely pathogenic ★★ same condition
CD46 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
CD46 p.Arg59Ter Pathogenic/Likely pathogenic ★★ same condition
CD46 p.Trp276Ter Pathogenic ★★ same condition
CD46 c.857-124T>A 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/cd46-p-ser287 (accessed [today's date]).

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