Is CLEC1B p.Val84Leu (c.250G>C) pathogenic?

CLEC1B p.Val84Leu (c.250G>C) is classified Likely benign in CLEC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.0885); Ultra-rare (popmax 0.0178%, nfe).

How common is CLEC1B p.Val84Leu (c.250G>C) in the general population?

CLEC1B p.Val84Leu (c.250G>C) is ultra-rare (popmax 0.0178%, nfe) (gnomAD).

What do computational predictors say about CLEC1B p.Val84Leu (c.250G>C)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

CLEC1B p.Val84Leu

c.250G>C · VCV3267678

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.2	GERP -2.5, phastCons 0.066
Regional constraint	o/e 1.04	unconstrained · MANE · 5,954 bp · p 0.53 · regional, not allelic
Overall
CADD	0.097	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 0.0178% European (non-Finnish) · 210/1,179,938 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0137% 221/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0178%	5,619
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.00167%	59,976
African / African-American	0.00133%	74,912

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.Val84Leu
Coding: c.250G>C
MANE Select: NM_138337 · reported on NM_016509
Type: single nucleotide variant
Location: chr12:9997193 (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-val84leu (accessed [today's date]).

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