Is CD300LG p.Pro22Ser (c.64C>T) pathogenic?

CD300LG p.Pro22Ser (c.64C>T) is classified Uncertain significance in CD300LG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: ambiguous (0.3845); Rare (popmax 0.204%, afr).

How common is CD300LG p.Pro22Ser (c.64C>T) in the general population?

CD300LG p.Pro22Ser (c.64C>T) is rare (popmax 0.204%, afr) (gnomAD).

What do computational predictors say about CD300LG p.Pro22Ser (c.64C>T)?

AlphaMissense predicts ambiguous (score 0.3845) — an in-silico prediction, not a clinical call.

CD300LG p.Pro22Ser

c.64C>T · rs146351601 · VCV2331095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3845 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.204%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3845	ambiguous
REVEL	0.165	moderately benign-leaning
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 15 kb · p 0.29 · regional, not allelic
Overall
CADD	23.5	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 0.204% African / African-American · 153/75,028 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.012% 193/1,613,932 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.204%	490
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,944
European (non-Finnish)	0.00186%	53,634

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.Pro22Ser
Coding: c.64C>T
MANE Select: NM_145273
dbSNP: rs146351601
Type: single nucleotide variant
Location: chr17:43848578 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.78
Residue 22: 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-pro22ser (accessed [today's date]).

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