Is CD300A p.Glu63Asp (c.189G>C) pathogenic?

CD300A p.Glu63Asp (c.189G>C) is classified Uncertain significance in CD300A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: ambiguous (0.4953); Very rare (popmax 0.005%, nfe).

How common is CD300A p.Glu63Asp (c.189G>C) in the general population?

CD300A p.Glu63Asp (c.189G>C) is very rare (popmax 0.005%, nfe) (gnomAD).

What do computational predictors say about CD300A p.Glu63Asp (c.189G>C)?

AlphaMissense predicts ambiguous (score 0.4953) — an in-silico prediction, not a clinical call.

CD300A p.Glu63Asp

c.189G>C · rs1198062594 · VCV3140507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4953	ambiguous
REVEL	0.154	moderately benign-leaning
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -0.26
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.069 · regional, not allelic
Overall
CADD	19.13	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 0.005% European (non-Finnish) · 59/1,180,056 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00366% 59/1,614,144 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: CD300A
Protein: p.Glu63Asp
Coding: c.189G>C
MANE Select: NM_007261
dbSNP: rs1198062594
Type: single nucleotide variant
Location: chr17:74473684 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.59 · 1 PDB
Residue 63: a disulfide bond; a β-strand; the ig-like v-type domain

Full CD300A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300A p.Ala6Thr Uncertain significance ★ ⚠ same type
CD300A p.Ala98Gly Uncertain significance ★ ⚠ same type
CD300A p.Arg262Gly Uncertain significance ★ ⚠ same type
CD300A p.Arg285Pro Uncertain significance ★ ⚠ same type
CD300A p.Asn176Tyr Uncertain significance ★ ⚠ same type
CD300A p.Cys103Tyr Uncertain significance ★ ⚠ same type
CD300A p.Cys15Tyr Uncertain significance ★ ⚠ same type
CD300A p.Glu173Asp 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/cd300a-p-glu63asp (accessed [today's date]).

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