Is CLEC18C p.Ser7Tyr (c.20C>A) pathogenic?

CLEC18C p.Ser7Tyr (c.20C>A) is classified Uncertain significance in CLEC18C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1151); Ultra-rare (popmax 0.0185%, afr).

How common is CLEC18C p.Ser7Tyr (c.20C>A) in the general population?

CLEC18C p.Ser7Tyr (c.20C>A) is ultra-rare (popmax 0.0185%, afr) (gnomAD).

What do computational predictors say about CLEC18C p.Ser7Tyr (c.20C>A)?

AlphaMissense predicts likely benign (score 0.1151) — an in-silico prediction, not a clinical call.

CLEC18C p.Ser7Tyr

c.20C>A · VCV4229729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1151 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1151	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -9.21	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 0.44	GERP 0.39
Regional constraint	o/e 0.12	constrained · MANE · 12 kb · p 1e-47 · regional, not allelic
Overall
CADD	13.19	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 0.0185% African / African-American · 11/59,394 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00803%

Overall 0.00294% 41/1,393,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0185%	5,399
European (non-Finnish)	0.00287%	34,884
South Asian	0.00115%	87,218

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.Ser7Tyr
Coding: c.20C>A
MANE Select: NM_173619
Type: single nucleotide variant
Location: chr16:70174298 (GRCh38)
Gene constraint: LOEUF 0.529 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 82.39

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-ser7tyr (accessed [today's date]).

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