Is CLEC18A p.Arg57Ser (c.169C>A) pathogenic?

CLEC18A p.Arg57Ser (c.169C>A) is classified Uncertain significance in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.4573); Absent from gnomAD v4.1.

How common is CLEC18A p.Arg57Ser (c.169C>A) in the general population?

CLEC18A p.Arg57Ser (c.169C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC18A p.Arg57Ser (c.169C>A)?

AlphaMissense predicts ambiguous (score 0.4573) — an in-silico prediction, not a clinical call.

CLEC18A p.Arg57Ser

c.169C>A · VCV4229708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4573 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 677,362)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4573	ambiguous
REVEL	0.137	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.01	constrained · MANE · 758 bp · p 3.7e-16 · regional, not allelic
Overall
CADD	25.4	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

No allele count reported in gnomAD v4.1 (AN 677,362). 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.Arg57Ser
Coding: c.169C>A
MANE Select: NM_001370523
Type: single nucleotide variant
Location: chr16:69952079 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 79.11
Residue 57: the scp domain

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

Similar variants

CLEC18A p.Arg57Cys Uncertain significance ★ ⚠ same residue
CLEC18A p.Arg57His Uncertain significance ★ ⚠ same residue
CLEC18A p.Arg57Leu Uncertain significance ★ ⚠ same residue
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

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-arg57ser (accessed [today's date]).

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