Is CD55 p.Val124Leu (c.370G>C) pathogenic?

CD55 p.Val124Leu (c.370G>C) is classified Uncertain significance in CD55 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: likely benign (0.2158); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CD55 p.Val124Leu (c.370G>C)?

CD55 p.Val124Leu (c.370G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CD55 p.Val124Leu (c.370G>C) in the general population?

CD55 p.Val124Leu (c.370G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD55 p.Val124Leu (c.370G>C)?

AlphaMissense predicts likely benign (score 0.2158) — an in-silico prediction, not a clinical call.

CD55 p.Val124Leu

c.370G>C · VCV4222958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2158	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4.4
Regional constraint	o/e 0.68	unconstrained · MANE · 4,298 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	0.07	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 0.00223% East Asian · 1/44,862 alleles

Overall 0.000657% 1/152,196 alleles · very rare

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.Val124Leu
Coding: c.370G>C
MANE Select: NM_000574
Type: single nucleotide variant
Location: chr1:207324642 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.99 · 33 PDB
Residue 124: a disulfide bond; the sushi 2 domain; a β-strand

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.Val124= 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-val124leu (accessed [today's date]).

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