Is CD55 p.Pro216Leu (c.647C>T) pathogenic?

CD55 p.Pro216Leu (c.647C>T) is classified Uncertain significance in CD55 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1378); Rare (popmax 0.122%, sas).

How common is CD55 p.Pro216Leu (c.647C>T) in the general population?

CD55 p.Pro216Leu (c.647C>T) is rare (popmax 0.122%, sas) (gnomAD).

What do computational predictors say about CD55 p.Pro216Leu (c.647C>T)?

AlphaMissense predicts likely benign (score 0.1378) — an in-silico prediction, not a clinical call.

CD55 p.Pro216Leu

c.647C>T · rs144692928 · VCV1403204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1378 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.122%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1378	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -9.79	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 -1.5	GERP -3.6
Regional constraint	o/e 0.68	unconstrained · MANE · 4,298 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	14.83	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 0.122% South Asian · 111/91,058 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0965%

Overall 0.00874% 141/1,613,280 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.122%	820
East Asian	0.0156%	6,409
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.004%	24,991
European (non-Finnish)	0.0011%	90,720

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.Pro216Leu
Coding: c.647C>T
MANE Select: NM_000574
dbSNP: rs144692928
Type: single nucleotide variant
Location: chr1:207326820 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 216: a disulfide bond; the sushi 3 domain; an α-helix

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

Similar variants

CD55 p.Pro216= Likely benign ★★ same residue
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

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-pro216leu (accessed [today's date]).

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