Is CD55 p.Pro166Leu (c.497C>T) pathogenic?

CD55 p.Pro166Leu (c.497C>T) is classified Uncertain significance in CD55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-27). AlphaMissense: ambiguous (0.5052); Very rare (popmax 0.00268%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD55 p.Pro166Leu (c.497C>T)?

CD55 p.Pro166Leu (c.497C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD55 p.Pro166Leu (c.497C>T) in the general population?

CD55 p.Pro166Leu (c.497C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about CD55 p.Pro166Leu (c.497C>T)?

AlphaMissense predicts ambiguous (score 0.5052) — an in-silico prediction, not a clinical call.

CD55 p.Pro166Leu

c.497C>T · rs201591726 · VCV1503478

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5052	ambiguous
REVEL	0.58	indeterminate
SaProt	LLR -13.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 4,298 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	27.4	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 0.00268% African / African-American · 2/74,606 alleles

Filtering AF 0.000882% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000721%

Overall 0.00168% 27/1,606,264 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00939%	10,648
African / African-Americangrpmax	0.00268%	37,303
Admixed American	0.00168%	59,576
Remaining individualsnot grpmax-eligible	0.00161%	62,228
European (non-Finnish)	0.00145%	69,089

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
Protein: p.Pro166Leu
Coding: c.497C>T
MANE Select: NM_000574
dbSNP: rs201591726
Type: single nucleotide variant
Location: chr1:207325640 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 166: a disulfide bond; the sushi 3 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD55 p.Pro166= Likely benign ★ same residue
CD55 p.Arg221Ser Uncertain significance ★★ ⚠ same condition
CD55 p.Asn171Ser Uncertain significance ★★ ⚠ same condition
CD55 p.Asn44Asp Uncertain significance ★★ ⚠ same condition
CD55 p.Glu273Gly Uncertain significance ★★ ⚠ same condition
CD55 p.His339Asn Uncertain significance ★★ ⚠ same condition
CD55 p.Leu374Val Uncertain significance ★★ ⚠ same condition
CD55 p.Met377Thr Uncertain significance ★★ ⚠ same condition

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-pro166leu (accessed [today's date]).

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