Is CD46 p.Ser13Phe (c.38C>T) pathogenic?

CD46 p.Ser13Phe (c.38C>T) is classified Benign/Likely benign in CD46 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1208); Low-frequency (popmax 3.81%, eas); Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CD46 p.Ser13Phe (c.38C>T)?

CD46 p.Ser13Phe (c.38C>T) is associated with atypical hemolytic-uremic syndrome, atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (ClinVar).

How common is CD46 p.Ser13Phe (c.38C>T) in the general population?

CD46 p.Ser13Phe (c.38C>T) is low-frequency (popmax 3.81%, eas) (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CD46 p.Ser13Phe (c.38C>T)?

AlphaMissense predicts likely benign (score 0.1208) — an in-silico prediction, not a clinical call.

CD46 p.Ser13Phe

c.38C>T · rs138843816 · VCV875708

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1208 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.81%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.1208	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -8.11	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 -5.7	GERP -2.2
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.012 · regional, not allelic
Overall
CADD	2.597	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

Grpmax group 3.81% East Asian · 1,710/44,878 alleles

Filtering AF 3.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.6%

Overall 0.207% 3,348/1,614,152 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.81%	26
Admixed American	1.14%	88
African / African-American	0.365%	274
South Asian	0.263%	380
Remaining individualsnot grpmax-eligible	0.248%	403
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0234%	4,275
Finnishnot grpmax-eligible	0.00938%	10,663

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.Ser13Phe
Coding: c.38C>T
MANE Select: NM_172351
dbSNP: rs138843816
Type: single nucleotide variant
Location: chr1:207752250 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 7 PDB
Residue 13: a UniProt-annotated variant site (in)

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

Disease context

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

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

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

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
CD46 p.Trp276Ter 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-ser13phe (accessed [today's date]).

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