Is CLEC18A p.Arg133Gln (c.398G>A) pathogenic?

CLEC18A p.Arg133Gln (c.398G>A) is classified Likely benign in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.036%, afr).

How common is CLEC18A p.Arg133Gln (c.398G>A) in the general population?

CLEC18A p.Arg133Gln (c.398G>A) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about CLEC18A p.Arg133Gln (c.398G>A)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CLEC18A p.Arg133Gln

c.398G>A · rs533136482 · VCV2564638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.23	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 -2.1	GERP -3.4
Regional constraint	o/e 0.66	unconstrained · MANE · 2,443 bp · p 0.00044 · regional, not allelic
Overall
CADD	0.259	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 0.036% African / African-American · 27/75,030 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00291% 47/1,612,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,779
Middle Eastern	0.0174%	5,736
Remaining individualsnot grpmax-eligible	0.0032%	31,210
East Asian	0.00223%	44,866
Admixed American	0.00167%	59,924
European (non-Finnish)	0.00127%	78,623

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: CLEC18A
Protein: p.Arg133Gln
Coding: c.398G>A
MANE Select: NM_001370523
dbSNP: rs533136482
Type: single nucleotide variant
Location: chr16:69954515 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 79.11
Residue 133: the scp domain

Full CLEC18A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18A p.Ala115Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala137Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala142Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala145Thr Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Ser Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala24Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala37Ser 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/clec18a-p-arg133gln (accessed [today's date]).

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