Is CD180 p.Gly545Val (c.1634G>T) pathogenic?

CD180 p.Gly545Val (c.1634G>T) is classified Uncertain significance in CD180 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.2158); Rare (popmax 0.264%, afr).

How common is CD180 p.Gly545Val (c.1634G>T) in the general population?

CD180 p.Gly545Val (c.1634G>T) is rare (popmax 0.264%, afr) (gnomAD).

What do computational predictors say about CD180 p.Gly545Val (c.1634G>T)?

AlphaMissense predicts likely benign (score 0.2158) — an in-silico prediction, not a clinical call.

CD180 p.Gly545Val

c.1634G>T · VCV4222618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2158 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.264%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2158	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.47	donor gain · deltas
Pangolin	Δ0.51	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 4.5, phastCons 0.61
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	22.2	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 0.264% African / African-American · 198/74,988 alleles

Filtering AF 0.234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.222%

Overall 0.0142% 229/1,612,798 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.264%	379
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Middle Eastern	0.0165%	6,060
Admixed American	0.015%	6,662
South Asian	0.0011%	90,984
European (non-Finnish)	0.000254%	393,015

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.Gly545Val
Coding: c.1634G>T
MANE Select: NM_005582
Type: single nucleotide variant
Location: chr5:67183209 (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-gly545val (accessed [today's date]).

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