Is CD46 p.Arg82Trp (c.244C>T) pathogenic?

CD46 p.Arg82Trp (c.244C>T) is classified Uncertain significance in CD46 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.2051); Ultra-rare (popmax 0.0156%, eas); Associated with CD46-related disorder.

What condition is associated with CD46 p.Arg82Trp (c.244C>T)?

CD46 p.Arg82Trp (c.244C>T) is associated with CD46-related disorder, atypical hemolytic-uremic syndrome with MCP/CD46 anomaly, atypical hemolytic-uremic syndrome (ClinVar).

How common is CD46 p.Arg82Trp (c.244C>T) in the general population?

CD46 p.Arg82Trp (c.244C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CD46 p.Arg82Trp (c.244C>T)?

AlphaMissense predicts likely benign (score 0.2051) — an in-silico prediction, not a clinical call.

CD46 p.Arg82Trp

c.244C>T · rs200133631 · VCV2202925

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD46-related disorder

Computational evidence

Protein change
AlphaMissense	0.2051	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.1
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.012 · regional, not allelic
Overall
CADD	18.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,864 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00285% 46/1,613,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
European (non-Finnish)	0.00305%	32,774
Remaining individualsnot grpmax-eligible	0.0016%	62,506
Finnishnot grpmax-eligible	0.00157%	63,874
African / African-American	0.00133%	74,988

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.Arg82Trp
Coding: c.244C>T
MANE Select: NM_172351
dbSNP: rs200133631
Type: single nucleotide variant
Location: chr1:207757160 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 7 PDB
Residue 82: a disulfide bond; the sushi 1 domain

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

Disease context

CD46-related disorder

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

Similar variants

CD46 p.Arg82Gln Uncertain significance ★★ ⚠ same residue
CD46 c.1082+2T>A Pathogenic ★★ same condition
CD46 c.286+1G>C Pathogenic/Likely 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.Phe242Cys Pathogenic/Likely pathogenic ★★ 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-arg82trp (accessed [today's date]).

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