Is CLEC18B p.Arg57His (c.170G>A) pathogenic?

CLEC18B p.Arg57His (c.170G>A) is classified Uncertain significance in CLEC18B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1401); Ultra-rare (popmax 0.0734%, eas).

How common is CLEC18B p.Arg57His (c.170G>A) in the general population?

CLEC18B p.Arg57His (c.170G>A) is ultra-rare (popmax 0.0734%, eas) (gnomAD).

What do computational predictors say about CLEC18B p.Arg57His (c.170G>A)?

AlphaMissense predicts likely benign (score 0.1401) — an in-silico prediction, not a clinical call.

CLEC18B p.Arg57His

c.170G>A · VCV4003519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1401 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1401	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.75	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 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 3,016 bp · p 5.3e-22 · regional, not allelic
Overall
CADD	25.0	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 0.0734% East Asian · 26/35,408 alleles

Filtering AF 0.0514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0441%

Overall 0.0105% 75/717,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0734%	1,362
South Asian	0.0496%	2,015
Remaining individualsnot grpmax-eligible	0.016%	6,261
European (non-Finnish)	0.00412%	24,279
African / African-American	0.00185%	54,112

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: CLEC18B
Protein: p.Arg57His
Coding: c.170G>A
MANE Select: NM_001385193
Type: single nucleotide variant
Location: chr16:74420547 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 57: the scp domain

Full CLEC18B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18B p.Arg57Cys Uncertain significance ★ ⚠ same residue
CLEC18B c.1212-212G>T Uncertain significance ★ ⚠ same type
CLEC18B p.Ala115Val Uncertain significance ★ ⚠ same type
CLEC18B p.Ala137Ser Uncertain significance ★ ⚠ same type
CLEC18B p.Ala137Thr Uncertain significance ★ ⚠ same type
CLEC18B p.Ala137Val Uncertain significance ★ ⚠ same type
CLEC18B p.Ala19Asp Uncertain significance ★ ⚠ same type
CLEC18B p.Ala202Val 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/clec18b-p-arg57his (accessed [today's date]).

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