Is CD300A p.Arg285Pro (c.854G>C) pathogenic?

CD300A p.Arg285Pro (c.854G>C) is classified Uncertain significance in CD300A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0362%, sas).

How common is CD300A p.Arg285Pro (c.854G>C) in the general population?

CD300A p.Arg285Pro (c.854G>C) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

What do computational predictors say about CD300A p.Arg285Pro (c.854G>C)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CD300A p.Arg285Pro

c.854G>C · VCV3998180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.64	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 -8.5	GERP -3.4
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.069 · regional, not allelic
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0362% South Asian · 33/91,078 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00204% 33/1,614,028 alleles · ultra-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.Arg285Pro
Coding: c.854G>C
MANE Select: NM_007261
Type: single nucleotide variant
Location: chr17:74484080 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.59 · 1 PDB
Residue 285: the 'disordered' region

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

Similar variants

CD300A p.Arg285Gln Likely benign ★ same residue
CD300A p.Ala6Thr Uncertain significance ★ ⚠ same type
CD300A p.Ala98Gly Uncertain significance ★ ⚠ same type
CD300A p.Arg262Gly 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-arg285pro (accessed [today's date]).

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