Is CLEC18B p.Ser7Pro (c.19T>C) pathogenic?

CLEC18B p.Ser7Pro (c.19T>C) is classified Uncertain significance in CLEC18B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0157%, eas).

How common is CLEC18B p.Ser7Pro (c.19T>C) in the general population?

CLEC18B p.Ser7Pro (c.19T>C) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

What do computational predictors say about CLEC18B p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

CLEC18B p.Ser7Pro

c.19T>C · rs756726066 · VCV2291675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.21	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 1.4	GERP 0.22, phastCons 0.001
Regional constraint	o/e 0.15	constrained · MANE · 81 bp · p 8.5e-07 · regional, not allelic
Overall
CADD	14.19	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

Grpmax group 0.0157% East Asian · 7/44,642 alleles

Filtering AF 0.00729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00517%

Overall 0.000435% 7/1,609,290 alleles · ultra-rare exomes 3/1,459,546 · genomes 4/149,744 · joint denominator

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.Ser7Pro
Coding: c.19T>C
MANE Select: NM_001385193
dbSNP: rs756726066
Type: single nucleotide variant
Location: chr16:74421252 (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-ser7pro (accessed [today's date]).

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