Is CD55 p.Ile223Asn (c.668T>A) pathogenic?

CD55 p.Ile223Asn (c.668T>A) is classified Benign in CD55 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.7182); Rare (popmax 0.315%, sas).

How common is CD55 p.Ile223Asn (c.668T>A) in the general population?

CD55 p.Ile223Asn (c.668T>A) is rare (popmax 0.315%, sas) (gnomAD).

What do computational predictors say about CD55 p.Ile223Asn (c.668T>A)?

AlphaMissense predicts likely pathogenic (score 0.7182) — an in-silico prediction, not a clinical call.

CD55 p.Ile223Asn

c.668T>A · rs551629921 · VCV1598647

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7182 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7182	likely pathogenic
REVEL	0.189	benign-leaning
SaProt	LLR -13.42	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 33 kb · p 0.17 · regional, not allelic
Overall
CADD	24.6	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 0.315% South Asian · 275/87,398 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.0182% 290/1,595,146 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.315%	318
Remaining individualsnot grpmax-eligible	0.0211%	4,748
African / African-American	0.0027%	37,101

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
Protein: p.Ile223Asn
Coding: c.668T>A
MANE Select: NM_000574
dbSNP: rs551629921
Type: single nucleotide variant
Location: chr1:207331111 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 223: the sushi 4 domain

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

Similar variants

CD55 c.286+1G>A Likely pathogenic ★★ same type
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
CD55 c.1081+1G>C Uncertain significance ★★ same type
CD55 p.Arg221Ser Uncertain significance ★★ ⚠ same type
CD55 p.Arg357Cys Uncertain significance ★★ ⚠ same type
CD55 p.Arg357His Uncertain significance ★★ ⚠ 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-p-ile223asn (accessed [today's date]).

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