Is CD180 p.Thr308Ile (c.923C>T) pathogenic?

CD180 p.Thr308Ile (c.923C>T) is classified Uncertain significance in CD180 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: ambiguous (0.4135); Very rare (popmax 8.47e-05%, nfe).

How common is CD180 p.Thr308Ile (c.923C>T) in the general population?

CD180 p.Thr308Ile (c.923C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD180 p.Thr308Ile (c.923C>T)?

AlphaMissense predicts ambiguous (score 0.4135) — an in-silico prediction, not a clinical call.

CD180 p.Thr308Ile

c.923C>T · rs1742119646 · VCV2560151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4135	ambiguous
REVEL	0.516	indeterminate
SaProt	LLR -10.33	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 4.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	19.91	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 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,876 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: CD180
Protein: p.Thr308Ile
Coding: c.923C>T
MANE Select: NM_005582
dbSNP: rs1742119646
Type: single nucleotide variant
Location: chr5:67183920 (GRCh38)
Gene constraint: LOEUF 1.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 1 PDB

Full CD180 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD180 p.Leu398= Benign ★★ same type
CD180 p.Ser584= Benign ★★ same type
CD180 p.Thr222= Benign ★★ same type
CD180 p.Thr430Ala Benign ★★ ⚠ same type
CD180 p.Ala415Ser Uncertain significance ★ ⚠ same type
CD180 p.Ala466Ser Uncertain significance ★ ⚠ same type
CD180 p.Ala649Thr Uncertain significance ★ ⚠ same type
CD180 p.Arg173Trp 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/cd180-p-thr308ile (accessed [today's date]).

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