Is CLEC18A p.Arg57His (c.170G>A) pathogenic?

CLEC18A p.Arg57His (c.170G>A) is classified Uncertain significance in CLEC18A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.108); Common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CLEC18A p.Arg57His (c.170G>A)?

AlphaMissense predicts likely benign (score 0.108) — an in-silico prediction, not a clinical call.

CLEC18A p.Arg57His

Q: How common is CLEC18A p.Arg57His (c.170G>A) in the general population?

CLEC18A p.Arg57His (c.170G>A) is common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.170G>A · rs796466650 · VCV2345492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.108 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.57%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.108	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.79	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.01	constrained · MANE · 758 bp · p 3.7e-16 · regional, not allelic
Overall
CADD	27.7	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 5.57% East Asian · 1,589/28,550 alleles

Filtering AF 5.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.25%

Overall 0.448% 3,012/672,186 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	5.57%	18
South Asian	2.48%	40
Remaining individualsnot grpmax-eligible	0.306%	327
Ashkenazi Jewishnot grpmax-eligible	0.3%	334
Middle Eastern	0.124%	805
African / African-American	0.0327%	3,055
European (non-Finnish)	0.0159%	6,278
Finnishnot grpmax-eligible	0.00896%	11,166
Admixed American	0.00393%	25,450

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.Arg57His
Coding: c.170G>A
MANE Select: NM_001370523
dbSNP: rs796466650
Type: single nucleotide variant
Location: chr16:69952080 (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.Arg57Leu Uncertain significance ★ ⚠ same residue
CLEC18A p.Arg57Ser 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-arg57his (accessed [today's date]).

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