Is CD46 p.Asp92= (c.276C>T) pathogenic?

CD46 p.Asp92= (c.276C>T) is classified Conflicting classifications of pathogenicity in CD46 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0533%, amr); Associated with atypical hemolytic-uremic syndrome with MCP/CD46 anomaly.

What condition is associated with CD46 p.Asp92= (c.276C>T)?

CD46 p.Asp92= (c.276C>T) is associated with atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (ClinVar).

How common is CD46 p.Asp92= (c.276C>T) in the general population?

CD46 p.Asp92= (c.276C>T) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

CD46 p.Asp92=

c.276C>T · rs148383499 · VCV294968

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Conditions

atypical hemolytic-uremic syndrome with MCP/CD46 anomaly

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 -20	GERP -2.8
Overall
CADD	0.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% Admixed American · 32/59,992 alleles

Filtering AF 0.0388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0345%

Overall 0.033% 532/1,612,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,875
European (non-Finnish)	0.0387%	2,587
Remaining individualsnot grpmax-eligible	0.0224%	4,461
African / African-American	0.0147%	6,809
South Asian	0.0121%	8,280
East Asian	0.0111%	8,976
Finnishnot grpmax-eligible	0.00472%	21,171

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.Asp92=
Coding: c.276C>T
MANE Select: NM_172351
dbSNP: rs148383499
Type: single nucleotide variant
Location: chr1:207757192 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 7 PDB
Residue 92: a disulfide bond; the sushi 1 domain; an α-helix

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

Disease context

atypical hemolytic-uremic syndrome with MCP/CD46 anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD46 p.Asp92Ala 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-asp92 (accessed [today's date]).

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