Is CD300A p.Pro247Leu (c.740C>T) pathogenic?

CD300A p.Pro247Leu (c.740C>T) is classified Uncertain significance in CD300A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely benign (0.0667); Ultra-rare (popmax 0.0268%, eas).

How common is CD300A p.Pro247Leu (c.740C>T) in the general population?

CD300A p.Pro247Leu (c.740C>T) is ultra-rare (popmax 0.0268%, eas) (gnomAD).

What do computational predictors say about CD300A p.Pro247Leu (c.740C>T)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

CD300A p.Pro247Leu

c.740C>T · VCV3488021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.45	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 -4.2	GERP -3.7
Regional constraint	o/e 0.90	unconstrained · MANE · 17 kb · p 0.069 · regional, not allelic
Overall
CADD	0.177	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 0.0268% East Asian · 12/44,838 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000744% 12/1,612,898 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.Pro247Leu
Coding: c.740C>T
MANE Select: NM_007261
Type: single nucleotide variant
Location: chr17:74481799 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.59 · 1 PDB

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-pro247leu (accessed [today's date]).

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