Is CD180 p.Ala415Ser (c.1243G>T) pathogenic?

CD180 p.Ala415Ser (c.1243G>T) is classified Uncertain significance in CD180 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely benign (0.1465); Ultra-rare (popmax 0.0165%, mid).

How common is CD180 p.Ala415Ser (c.1243G>T) in the general population?

CD180 p.Ala415Ser (c.1243G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD180 p.Ala415Ser (c.1243G>T)?

AlphaMissense predicts likely benign (score 0.1465) — an in-silico prediction, not a clinical call.

CD180 p.Ala415Ser

c.1243G>T · rs769368678 · VCV2280703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1465 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1465	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -4.64	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 7.7	GERP 6.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000684% 10/1,461,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.0134%	7,481
South Asian	0.0022%	45,542
European (non-Finnish)	8.47e-05%	1,180,012

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.Ala415Ser
Coding: c.1243G>T
MANE Select: NM_005582
dbSNP: rs769368678
Type: single nucleotide variant
Location: chr5:67183600 (GRCh38)
Gene constraint: LOEUF 1.886 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.27 · 1 PDB
Residue 415: a turn

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.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-ala415ser (accessed [today's date]).

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