Is CLEC18C p.Gln83Pro (c.248A>C) pathogenic?

CLEC18C p.Gln83Pro (c.248A>C) is classified Uncertain significance in CLEC18C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.2379); Very rare (popmax 0.000426%, nfe).

How common is CLEC18C p.Gln83Pro (c.248A>C) in the general population?

CLEC18C p.Gln83Pro (c.248A>C) is very rare (popmax 0.000426%, nfe) (gnomAD).

What do computational predictors say about CLEC18C p.Gln83Pro (c.248A>C)?

AlphaMissense predicts likely benign (score 0.2379) — an in-silico prediction, not a clinical call.

CLEC18C p.Gln83Pro

c.248A>C · VCV4654268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2379 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000426%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2379	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -12.21	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 6.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 12 kb · p 1e-47 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.000426% European (non-Finnish) · 5/1,172,938 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000314% 5/1,591,610 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: CLEC18C
Protein: p.Gln83Pro
Coding: c.248A>C
MANE Select: NM_173619
Type: single nucleotide variant
Location: chr16:70177272 (GRCh38)
Gene constraint: LOEUF 0.529 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 82.39
Residue 83: the scp domain

Full CLEC18C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC18C p.Ala137Gly Uncertain significance ★ ⚠ same type
CLEC18C p.Ala145Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Ala40Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Ala413Ser Uncertain significance ★ ⚠ same type
CLEC18C p.Ala66Glu Uncertain significance ★ ⚠ same type
CLEC18C p.Ala84Thr Uncertain significance ★ ⚠ same type
CLEC18C p.Arg102Cys Uncertain significance ★ ⚠ same type
CLEC18C p.Arg143Cys 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/clec18c-p-gln83pro (accessed [today's date]).

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