Is CLEC18B p.Ile284Val (c.850A>G) pathogenic?

CLEC18B p.Ile284Val (c.850A>G) is classified Likely benign in CLEC18B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0583); Ultra-rare (popmax 0.023%, sas).

How common is CLEC18B p.Ile284Val (c.850A>G) in the general population?

CLEC18B p.Ile284Val (c.850A>G) is ultra-rare (popmax 0.023%, sas) (gnomAD).

What do computational predictors say about CLEC18B p.Ile284Val (c.850A>G)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

CLEC18B p.Ile284Val

c.850A>G · VCV4003524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -4.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.7	GERP -3.4
Regional constraint	o/e 0.01	constrained · MANE · 4,052 bp · p 4.3e-68 · regional, not allelic
Overall
CADD	0.005	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 0.023% South Asian · 20/86,954 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.00524% 81/1,545,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.023%	4,348
European (non-Finnish)	0.0053%	18,865
Remaining individualsnot grpmax-eligible	0.00167%	59,950

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.Ile284Val
Coding: c.850A>G
MANE Select: NM_001385193
Type: single nucleotide variant
Location: chr16:74412181 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28

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-ile284val (accessed [today's date]).

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