Is CD55 p.Arg130His (c.389G>A) pathogenic?

CD55 p.Arg130His (c.389G>A) is classified Uncertain significance in CD55 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-09). AlphaMissense: ambiguous (0.3835); Very rare (popmax 0.00334%, amr).

How common is CD55 p.Arg130His (c.389G>A) in the general population?

CD55 p.Arg130His (c.389G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CD55 p.Arg130His (c.389G>A)?

AlphaMissense predicts ambiguous (score 0.3835) — an in-silico prediction, not a clinical call.

CD55 p.Arg130His

c.389G>A · rs756646491 · VCV1016434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
AlphaMissense	0.3835	ambiguous
REVEL	0.442	indeterminate
SaProt	LLR -10.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.3, phastCons 0.92
Regional constraint	o/e 0.68	unconstrained · MANE · 4,298 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	21.4	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 0.00334% Admixed American · 2/59,860 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00149% 24/1,612,506 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,930
Remaining individualsnot grpmax-eligible	0.0032%	31,212
European (non-Finnish)	0.0017%	58,956

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.Arg130His
Coding: c.389G>A
MANE Select: NM_000574
dbSNP: rs756646491
Type: single nucleotide variant
Location: chr1:207324661 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 130: a disulfide bond; the sushi 2 domain

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

Similar variants

CD55 p.Arg130Ser Uncertain significance ★ ⚠ 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-arg130his (accessed [today's date]).

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