Is CLEC18B p.Ala37Val (c.110C>T) pathogenic?

CLEC18B p.Ala37Val (c.110C>T) is classified Likely benign in CLEC18B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-21). AlphaMissense: likely benign (0.0671); Ultra-rare (popmax 0.0692%, afr).

How common is CLEC18B p.Ala37Val (c.110C>T) in the general population?

CLEC18B p.Ala37Val (c.110C>T) is ultra-rare (popmax 0.0692%, afr) (gnomAD).

What do computational predictors say about CLEC18B p.Ala37Val (c.110C>T)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

CLEC18B p.Ala37Val

c.110C>T · VCV4003522

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0692%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.64	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 0.62	GERP -0.82
Regional constraint	o/e 0.00	constrained · MANE · 3,016 bp · p 5.3e-22 · regional, not allelic
Overall
CADD	3.244	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 0.0692% African / African-American · 51/73,704 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.00323% 52/1,608,344 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0692%	1,445
Remaining individualsnot grpmax-eligible	0.00161%	62,248

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.Ala37Val
Coding: c.110C>T
MANE Select: NM_001385193
Type: single nucleotide variant
Location: chr16:74421161 (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-ala37val (accessed [today's date]).

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