Is CLEC18A p.Pro64Ala (c.190C>G) pathogenic?

CLEC18A p.Pro64Ala (c.190C>G) is classified Uncertain significance in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.2431); No allele count reported in gnomAD v4.1 (AN 609,172).

How common is CLEC18A p.Pro64Ala (c.190C>G) in the general population?

CLEC18A p.Pro64Ala (c.190C>G) is no allele count reported in gnomAD v4.1 (AN 609,172) (gnomAD).

What do computational predictors say about CLEC18A p.Pro64Ala (c.190C>G)?

AlphaMissense predicts likely benign (score 0.2431) — an in-silico prediction, not a clinical call.

CLEC18A p.Pro64Ala

c.190C>G · VCV4003515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2431 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 609,172)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2431	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.01	constrained · MANE · 758 bp · p 3.7e-16 · regional, not allelic
Overall
CADD	24.7	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

No allele count reported in gnomAD v4.1 (AN 609,172). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLEC18A
Protein: p.Pro64Ala
Coding: c.190C>G
MANE Select: NM_001370523
Type: single nucleotide variant
Location: chr16:69952100 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 79.11
Residue 64: the scp domain

Full CLEC18A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18A p.Ala115Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala137Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala142Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala145Thr Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Ser Uncertain significance ★ ⚠ same type
CLEC18A p.Ala19Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala24Val Uncertain significance ★ ⚠ same type
CLEC18A p.Ala37Ser 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/clec18a-p-pro64ala (accessed [today's date]).

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