Is CLEC18B p.His239Arg (c.716A>G) pathogenic?

CLEC18B p.His239Arg (c.716A>G) is classified Uncertain significance in CLEC18B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.02%, eas).

How common is CLEC18B p.His239Arg (c.716A>G) in the general population?

CLEC18B p.His239Arg (c.716A>G) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about CLEC18B p.His239Arg (c.716A>G)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CLEC18B p.His239Arg

c.716A>G · rs777864675 · VCV3145623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.20	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 1.5	GERP -2.6, phastCons 0.96
Regional constraint	o/e 0.01	constrained · MANE · 4,052 bp · p 4.3e-68 · regional, not allelic
Overall
CADD	7.199	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 0.02% East Asian · 9/44,898 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00341% 55/1,611,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,989
Remaining individualsnot grpmax-eligible	0.00803%	12,458
Admixed American	0.00667%	14,997
African / African-American	0.00401%	24,960
South Asian	0.0033%	30,333
European (non-Finnish)	0.00263%	38,057

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.His239Arg
Coding: c.716A>G
MANE Select: NM_001385193
dbSNP: rs777864675
Type: single nucleotide variant
Location: chr16:74412841 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 239: the egf-like domain; a disulfide bond

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

Similar variants

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
CLEC18B p.Ala66Glu 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-his239arg (accessed [today's date]).

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