Is CLEC17A p.Pro116Thr (c.346C>A) pathogenic?

CLEC17A p.Pro116Thr (c.346C>A) is classified Uncertain significance in CLEC17A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.0831); Ultra-rare (popmax 0.0213%, afr).

How common is CLEC17A p.Pro116Thr (c.346C>A) in the general population?

CLEC17A p.Pro116Thr (c.346C>A) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about CLEC17A p.Pro116Thr (c.346C>A)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

CLEC17A p.Pro116Thr

c.346C>A · rs376222790 · VCV2470025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -8.48	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 -1.5	GERP -2.3
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.03 · regional, not allelic
Overall
CADD	0.73	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 0.0213% African / African-American · 16/75,024 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000991% 16/1,613,974 alleles · ultra-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: CLEC17A
Protein: p.Pro116Thr
Coding: c.346C>A
MANE Select: NM_001204118
dbSNP: rs376222790
Type: single nucleotide variant
Location: chr19:14594667 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.08
Residue 116: the 'disordered' region

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

Similar variants

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
CLEC17A p.Asp228Asn 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-pro116thr (accessed [today's date]).

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