Is CD55 p.Arg357His (c.1070G>A) pathogenic?

CD55 p.Arg357His (c.1070G>A) is classified Uncertain significance in CD55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-07). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.033%, mid).

How common is CD55 p.Arg357His (c.1070G>A) in the general population?

CD55 p.Arg357His (c.1070G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CD55 p.Arg357His (c.1070G>A)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

CD55 p.Arg357His

c.1070G>A · rs148720717 · VCV1697180

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.92	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 -14	GERP -2.5
Regional constraint	o/e 0.90	unconstrained · MANE · 33 kb · p 0.17 · regional, not allelic
Overall
CADD	0.002	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 0.033% Middle Eastern · 2/6,066 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.00461% 74/1,605,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,033
South Asian	0.0235%	4,262
African / African-American	0.0121%	8,274
European (non-Finnish)	0.0034%	29,410
East Asian	0.00225%	44,440
Remaining individualsnot grpmax-eligible	0.00161%	62,056

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.Arg357His
Coding: c.1070G>A
MANE Select: NM_000574
dbSNP: rs148720717
Type: single nucleotide variant
Location: chr1:207339406 (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

Similar variants

CD55 p.Arg357Cys 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.Asn171Ser 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-arg357his (accessed [today's date]).

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