Is CLEC18A p.Pro114Arg (c.341C>G) pathogenic?

CLEC18A p.Pro114Arg (c.341C>G) is classified Uncertain significance in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1389); Very rare (popmax 0.000514%, nfe).

How common is CLEC18A p.Pro114Arg (c.341C>G) in the general population?

CLEC18A p.Pro114Arg (c.341C>G) is very rare (popmax 0.000514%, nfe) (gnomAD).

What do computational predictors say about CLEC18A p.Pro114Arg (c.341C>G)?

AlphaMissense predicts likely benign (score 0.1389) — an in-silico prediction, not a clinical call.

CLEC18A p.Pro114Arg

c.341C>G · rs1340291007 · VCV2316417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1389 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000514%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1389	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 2,443 bp · p 0.00044 · regional, not allelic
Overall
CADD	22.2	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 0.000514% European (non-Finnish) · 6/1,167,198 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000416% 6/1,443,982 alleles · very rare

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: CLEC18A
Protein: p.Pro114Arg
Coding: c.341C>G
MANE Select: NM_001370523
dbSNP: rs1340291007
Type: single nucleotide variant
Location: chr16:69954458 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 79.11
Residue 114: 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-pro114arg (accessed [today's date]).

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