Is CD55 p.Val333Ile (c.997G>A) pathogenic?

CD55 p.Val333Ile (c.997G>A) is classified Benign/Likely benign in CD55 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0823); Rare (popmax 0.738%, afr).

How common is CD55 p.Val333Ile (c.997G>A) in the general population?

CD55 p.Val333Ile (c.997G>A) is rare (popmax 0.738%, afr) (gnomAD).

What do computational predictors say about CD55 p.Val333Ile (c.997G>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

CD55 p.Val333Ile

c.997G>A · rs116473488 · VCV1598556

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.738%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.87	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 1.3	GERP 0.58, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 33 kb · p 0.17 · regional, not allelic
Overall
CADD	2.703	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 0.738% African / African-American · 553/74,910 alleles

Filtering AF 0.687% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.667%

Overall 0.0374% 602/1,609,918 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.738%	135
Remaining individualsnot grpmax-eligible	0.0497%	2,011
Admixed American	0.025%	4,000
European (non-Finnish)	0.000255%	392,102

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.Val333Ile
Coding: c.997G>A
MANE Select: NM_000574
dbSNP: rs116473488
Type: single nucleotide variant
Location: chr1:207337346 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 333: the 'disordered' region

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-val333ile (accessed [today's date]).

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