Is CD300LG p.Cys61Gly (c.181T>G) pathogenic?

CD300LG p.Cys61Gly (c.181T>G) is classified Uncertain significance in CD300LG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely pathogenic (0.8661); Very rare (popmax 0.000593%, nfe).

How common is CD300LG p.Cys61Gly (c.181T>G) in the general population?

CD300LG p.Cys61Gly (c.181T>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CD300LG p.Cys61Gly (c.181T>G)?

AlphaMissense predicts likely pathogenic (score 0.8661) — an in-silico prediction, not a clinical call.

CD300LG p.Cys61Gly

c.181T>G · rs1176291045 · VCV2222378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8661	likely pathogenic · top 4% in CD300LG
REVEL	0.241	benign-leaning
SaProt	LLR -15.96	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 15 kb · p 0.29 · regional, not allelic
Overall
CADD	24.1	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 0.000593% European (non-Finnish) · 7/1,180,038 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,038 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: CD300LG
Protein: p.Cys61Gly
Coding: c.181T>G
MANE Select: NM_145273
dbSNP: rs1176291045
Type: single nucleotide variant
Location: chr17:43848695 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.78
Residue 61: a disulfide bond; the ig-like v-type domain

Full CD300LG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300LG p.Ala142Pro Uncertain significance ★ ⚠ same type
CD300LG p.Ala179Ser Uncertain significance ★ ⚠ same type
CD300LG p.Ala181Val Uncertain significance ★ ⚠ same type
CD300LG p.Ala211Ser Uncertain significance ★ ⚠ same type
CD300LG p.Ala266Thr Uncertain significance ★ ⚠ same type
CD300LG p.Ala266Val Uncertain significance ★ ⚠ same type
CD300LG p.Ala332Ser Uncertain significance ★ ⚠ same type
CD300LG p.Arg112Gln 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/cd300lg-p-cys61gly (accessed [today's date]).

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