Is CLEC17A p.Glu74Asp (c.222G>T) pathogenic?

CLEC17A p.Glu74Asp (c.222G>T) is classified Likely benign in CLEC17A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.073); Very rare (popmax 0.00699%, amr).

How common is CLEC17A p.Glu74Asp (c.222G>T) in the general population?

CLEC17A p.Glu74Asp (c.222G>T) is very rare (popmax 0.00699%, amr) (gnomAD).

What do computational predictors say about CLEC17A p.Glu74Asp (c.222G>T)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

CLEC17A p.Glu74Asp

c.222G>T · rs567554376 · VCV2383315

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00699%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -9.20	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 -11	GERP -2.5
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.03 · regional, not allelic
Overall
CADD	0.005	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 0.00699% Admixed American · 4/57,230 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.00431% 69/1,600,880 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00699%	14,308
European (non-Finnish)	0.00537%	18,632
Remaining individualsnot grpmax-eligible	0.00322%	31,019

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: CLEC17A
Protein: p.Glu74Asp
Coding: c.222G>T
MANE Select: NM_001204118
dbSNP: rs567554376
Type: single nucleotide variant
Location: chr19:14592303 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.08
Residue 74: the 'disordered' region

Full CLEC17A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC17A p.Glu74Lys Uncertain significance ★ ⚠ same residue
CLEC17A p.Arg158Met Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250Cys Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250His Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250Pro Uncertain significance ★ ⚠ same type
CLEC17A p.Asn137Lys Uncertain significance ★ ⚠ same type
CLEC17A p.Asn3Asp Uncertain significance ★ ⚠ same type
CLEC17A p.Asp123Gly 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/clec17a-p-glu74asp (accessed [today's date]).

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