Is CD180 p.Thr306Pro (c.916A>C) pathogenic?

CD180 p.Thr306Pro (c.916A>C) is classified Uncertain significance in CD180 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: ambiguous (0.5139); Ultra-rare (popmax 0.0307%, sas).

How common is CD180 p.Thr306Pro (c.916A>C) in the general population?

CD180 p.Thr306Pro (c.916A>C) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

What do computational predictors say about CD180 p.Thr306Pro (c.916A>C)?

AlphaMissense predicts ambiguous (score 0.5139) — an in-silico prediction, not a clinical call.

CD180 p.Thr306Pro

c.916A>C · rs766257363 · VCV2623761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

Computational evidence

Protein change
AlphaMissense	0.5139	ambiguous
REVEL	0.294	indeterminate
SaProt	LLR -11.72	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 4.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	24.2	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 0.0307% South Asian · 28/91,088 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00173% 28/1,614,092 alleles · ultra-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.Thr306Pro
Coding: c.916A>C
MANE Select: NM_005582
dbSNP: rs766257363
Type: single nucleotide variant
Location: chr5:67183927 (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-thr306pro (accessed [today's date]).

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