Is CLEC1B p.Val46Phe (c.136G>T) pathogenic?

CLEC1B p.Val46Phe (c.136G>T) is classified Uncertain significance in CLEC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0935); Very rare (popmax 0.00475%, nfe).

How common is CLEC1B p.Val46Phe (c.136G>T) in the general population?

CLEC1B p.Val46Phe (c.136G>T) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about CLEC1B p.Val46Phe (c.136G>T)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

CLEC1B p.Val46Phe

c.136G>T · rs199738622 · VCV2366472

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.30	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	7.578	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 0.00475% European (non-Finnish) · 56/1,180,022 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.0289% 466/1,614,112 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.24%	81
Remaining individualsnot grpmax-eligible	0.064%	1,563
European (non-Finnish)grpmax	0.00475%	21,072
African / African-American	0.004%	24,998
Admixed American	0.00167%	60,022

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CLEC1B
Protein: p.Val46Phe
Coding: c.136G>T
MANE Select: NM_138337 · reported on NM_016509
dbSNP: rs199738622
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-val46phe (accessed [today's date]).

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