Is CD180 p.Val5Ile (c.13G>A) pathogenic?

CD180 p.Val5Ile (c.13G>A) is classified Uncertain significance in CD180 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-30). AlphaMissense: likely benign (0.0679); Ultra-rare (popmax 0.0267%, afr).

How common is CD180 p.Val5Ile (c.13G>A) in the general population?

CD180 p.Val5Ile (c.13G>A) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about CD180 p.Val5Ile (c.13G>A)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

CD180 p.Val5Ile

c.13G>A · VCV3264744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -6.43	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 -0.85	GERP 0.34
Regional constraint	o/e 0.94	unconstrained · MANE · 14 kb · p 0.097 · regional, not allelic
Overall
CADD	0.599	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 0.0267% African / African-American · 20/74,846 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00874% 141/1,613,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,742
Admixed American	0.01%	9,996
European (non-Finnish)	0.00924%	10,825
East Asian	0.00446%	22,440
South Asian	0.00329%	30,356
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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.Val5Ile
Coding: c.13G>A
MANE Select: NM_005582
Type: single nucleotide variant
Location: chr5:67196629 (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-val5ile (accessed [today's date]).

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