Is CD200 p.Leu122Phe (c.364C>T) pathogenic?

CD200 p.Leu122Phe (c.364C>T) is classified Uncertain significance in CD200 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). Ultra-rare (popmax 0.0169%, nfe).

How common is CD200 p.Leu122Phe (c.364C>T) in the general population?

CD200 p.Leu122Phe (c.364C>T) is ultra-rare (popmax 0.0169%, nfe) (gnomAD).

CD200 p.Leu122Phe

c.364C>T · VCV3829437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.25	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 28 kb · p 0.00055 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% European (non-Finnish) · 200/1,179,958 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0126% 204/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0169%	5,900
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: CD200
Protein: p.Leu122Phe
Coding: c.364C>T
MANE Select: NM_005944
Type: single nucleotide variant
Location: chr3:112345231 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 86.39
Residue 122: a disulfide bond; the ig-like v-type domain

Full CD200 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD200 c.12+2787T>A Uncertain significance ★ same type
CD200 p.Ala23Val Uncertain significance ★ same type
CD200 p.Arg261His Uncertain significance ★ same type
CD200 p.Arg3Thr Uncertain significance ★ same type
CD200 p.Asn157Ser Uncertain significance ★ same type
CD200 p.Asn55Lys Uncertain significance ★ same type
CD200 p.Asn81Lys Uncertain significance ★ same type
CD200 p.Gln42His 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/cd200-p-leu122phe (accessed [today's date]).

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