Is CD300E p.Cys50Arg (c.148T>C) pathogenic?

CD300E p.Cys50Arg (c.148T>C) is classified Uncertain significance in CD300E (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.9233); Ultra-rare (popmax 0.0107%, afr).

How common is CD300E p.Cys50Arg (c.148T>C) in the general population?

CD300E p.Cys50Arg (c.148T>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CD300E p.Cys50Arg (c.148T>C)?

AlphaMissense predicts likely pathogenic (score 0.9233) — an in-silico prediction, not a clinical call.

CD300E p.Cys50Arg

c.148T>C · rs1010053993 · VCV2589880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9233 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9233	likely pathogenic · top 2% in CD300E
REVEL	0.541	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.29 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0107% African / African-American · 8/74,858 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,613,924 alleles · ultra-rare exomes 2/1,461,884 · genomes 6/152,040 · joint denominator

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: CD300E
Protein: p.Cys50Arg
Coding: c.148T>C
MANE Select: NM_181449
dbSNP: rs1010053993
Type: single nucleotide variant
Location: chr17:74617358 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.04
Residue 50: the ig-like v-type domain

Full CD300E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300E p.Ala130Glu Uncertain significance ★ ⚠ same type
CD300E p.Ala99Thr Uncertain significance ★ ⚠ same type
CD300E p.Arg168Gln Uncertain significance ★ ⚠ same type
CD300E p.Arg51Leu Uncertain significance ★ same type
CD300E p.Asn150Lys Uncertain significance ★ ⚠ same type
CD300E p.Glu39Lys Uncertain significance ★ ⚠ same type
CD300E p.Leu16Phe Uncertain significance ★ ⚠ same type
CD300E p.Pro134Leu 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/cd300e-p-cys50arg (accessed [today's date]).

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