Is CD180 p.Thr430Ala (c.1288A>G) pathogenic?

CD180 p.Thr430Ala (c.1288A>G) is classified Benign in CD180 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-12). AlphaMissense: likely benign (0.2577); Common (popmax 5.89%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD180 p.Thr430Ala (c.1288A>G)?

AlphaMissense predicts likely benign (score 0.2577) — an in-silico prediction, not a clinical call.

CD180 p.Thr430Ala

Q: How common is CD180 p.Thr430Ala (c.1288A>G) in the general population?

CD180 p.Thr430Ala (c.1288A>G) is common (popmax 5.89%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1288A>G · rs2230523 · VCV787819

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2577 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.89%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2577	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 6.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	23.8	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 5.89% African / African-American · 4,415/75,004 alleles

Filtering AF 5.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.68%

Overall 0.312% 5,033/1,614,134 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.89%	17
Admixed American	0.416%	240
Remaining individualsnot grpmax-eligible	0.392%	255
Middle Eastern	0.28%	357
South Asian	0.0143%	7,005
European (non-Finnish)	0.00771%	12,967
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,890

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.Thr430Ala
Coding: c.1288A>G
MANE Select: NM_005582
dbSNP: rs2230523
Type: single nucleotide variant
Location: chr5:67183555 (GRCh38)
Gene constraint: LOEUF 1.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 1 PDB
Residue 430: a UniProt-annotated variant site (in)

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.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
CD180 p.Arg472Trp 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-thr430ala (accessed [today's date]).

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