Is CLEC16A p.Pro894Ser (c.2680C>T) pathogenic?

CLEC16A p.Pro894Ser (c.2680C>T) is classified Uncertain significance in CLEC16A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-03). AlphaMissense: likely benign (0.0594); Absent from gnomAD v4.1.

How common is CLEC16A p.Pro894Ser (c.2680C>T) in the general population?

CLEC16A p.Pro894Ser (c.2680C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC16A p.Pro894Ser (c.2680C>T)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

CLEC16A p.Pro894Ser

c.2680C>T · VCV3833898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,416)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -5.25	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 -0.056	GERP 0.47
Regional constraint	o/e 1.05	unconstrained · MANE · 199 kb · p 0.087 · regional, not allelic
Overall
CADD	1.145	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

No allele count reported in gnomAD v4.1 (AN 1,606,416). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLEC16A
Protein: p.Pro894Ser
Coding: c.2680C>T
MANE Select: NM_015226
Type: single nucleotide variant
Location: chr16:11166426 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.17
Residue 894: the 'disordered' region

Full CLEC16A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC16A p.Pro894Leu Uncertain significance ★ ⚠ same residue
CLEC16A p.Glu432= Benign/Likely benign ★★ same type
CLEC16A p.His31= Likely benign ★★ same type
CLEC16A p.Leu948Phe Benign ★★ same type
CLEC16A p.Ser892Asn Likely benign ★★ same type
CLEC16A p.Ser982Asn Likely benign ★★ same type
CLEC16A p.Thr475Met Benign/Likely benign ★★ same type
CLEC16A p.Ala1043Val 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/clec16a-p-pro894ser (accessed [today's date]).

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