Is CD55 c.286+1G>A pathogenic?

CD55 c.286+1G>A is classified Likely pathogenic in CD55 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-06). Very rare (popmax 0.00316%, nfe); Associated with CD55-related disorder.

What condition is associated with CD55 c.286+1G>A?

CD55 c.286+1G>A is associated with CD55-related disorder (ClinVar).

How common is CD55 c.286+1G>A in the general population?

CD55 c.286+1G>A is very rare (popmax 0.00316%, nfe) (gnomAD).

CD55 c.286+1G>A

rs376304458 · VCV1520269

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00316%, nfe)

Conditions

CD55-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss · deltas
Pangolin	Δ0.89	loss · gain 0.50 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5	GERP 1.5, phastCons 1
Non-coding constraint	Z 1.44	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00316% European (non-Finnish) · 37/1,172,406 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00203%

Overall 0.00263% 42/1,593,976 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00628%	15,921
European (non-Finnish)grpmax	0.00316%	31,687
Remaining individualsnot grpmax-eligible	0.00163%	61,530

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CD55
Coding: c.286+1G>A
MANE Select: NM_000574
dbSNP: rs376304458
Type: single nucleotide variant
Location: chr1:207322568 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB

Full CD55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD55-related disorder

Similar variants

CD55 c.101-2A>C Likely pathogenic ★ same condition
CD55 c.1082-2A>G Likely pathogenic ★ same condition
CD55 p.Gln173Ter Likely pathogenic ★ same condition
CD55 p.Met1Leu Likely pathogenic ★ same condition
CD55 p.Met1Thr Likely pathogenic ★ same condition
CD55 c.286+2T>G Likely pathogenic ★★ same type
CD55 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same type
CD55 p.Trp213Ter Pathogenic/Likely pathogenic ★★ same type

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/cd55-c-286-plus-1g-a (accessed [today's date]).

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