Is CLEC1B p.Val46Ile (c.136G>A) pathogenic?

CLEC1B p.Val46Ile (c.136G>A) is classified Uncertain significance in CLEC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely benign (0.081); Absent from gnomAD v4.1.

How common is CLEC1B p.Val46Ile (c.136G>A) in the general population?

CLEC1B p.Val46Ile (c.136G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC1B p.Val46Ile (c.136G>A)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

CLEC1B p.Val46Ile

c.136G>A · VCV3493558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.3	GERP -3.2
Regional constraint	o/e 1.04	unconstrained · MANE · 5,954 bp · p 0.53 · regional, not allelic
Overall
CADD	0.123	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLEC1B
Protein: p.Val46Ile
Coding: c.136G>A
MANE Select: NM_138337 · reported on NM_016509
Type: single nucleotide variant
Location: chr12:9998309 (GRCh38)

Full CLEC1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/clec1b-p-val46ile (accessed [today's date]).

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