Is CD300LB p.His146Tyr (c.436C>T) pathogenic?

CD300LB p.His146Tyr (c.436C>T) is classified Likely benign in CD300LB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0738); Very rare (popmax 0.000255%, nfe).

How common is CD300LB p.His146Tyr (c.436C>T) in the general population?

CD300LB p.His146Tyr (c.436C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CD300LB p.His146Tyr (c.436C>T)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

CD300LB p.His146Tyr

c.436C>T · rs2509526415 · VCV3140524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.31	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 -1.1	GERP -2.2
Regional constraint	o/e 0.88	unconstrained · MANE · 8,609 bp · p 0.06 · regional, not allelic
Overall
CADD	0.004	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 0.000255% European (non-Finnish) · 3/1,177,540 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,459,152 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: CD300LB
Protein: p.His146Tyr
Coding: c.436C>T
MANE Select: NM_174892
dbSNP: rs2509526415
Type: single nucleotide variant
Location: chr17:74523586 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.23

Full CD300LB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300LB c.-14G>T Uncertain significance ★ same type
CD300LB c.-42T>A Uncertain significance ★ same type
CD300LB c.-59G>T Uncertain significance ★ same type
CD300LB p.Ala26Ser Uncertain significance ★ ⚠ same type
CD300LB p.Ala26Val Uncertain significance ★ ⚠ same type
CD300LB p.Arg177Gly Uncertain significance ★ ⚠ same type
CD300LB p.Arg25Thr Uncertain significance ★ ⚠ same type
CD300LB p.Arg51Gln 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/cd300lb-p-his146tyr (accessed [today's date]).

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