Is CLEC16A p.Asp865Val (c.2594A>T) pathogenic?

CLEC16A p.Asp865Val (c.2594A>T) is classified Uncertain significance in CLEC16A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.361); Very rare (popmax 8.48e-05%, nfe).

How common is CLEC16A p.Asp865Val (c.2594A>T) in the general population?

CLEC16A p.Asp865Val (c.2594A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CLEC16A p.Asp865Val (c.2594A>T)?

AlphaMissense predicts ambiguous (score 0.361) — an in-silico prediction, not a clinical call.

CLEC16A p.Asp865Val

c.2594A>T · rs2510708904 · VCV3145588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.361	ambiguous
REVEL	0.35	indeterminate
SaProt	LLR -4.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 199 kb · p 0.087 · regional, not allelic
Overall
CADD	25.0	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 8.48e-05% European (non-Finnish) · 1/1,179,736 alleles

Overall 6.84e-05% 1/1,461,686 alleles · very 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: CLEC16A
Protein: p.Asp865Val
Coding: c.2594A>T
MANE Select: NM_015226
dbSNP: rs2510708904
Type: single nucleotide variant
Location: chr16:11126099 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.17

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

Similar variants

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
CLEC16A p.Ala347Thr 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-asp865val (accessed [today's date]).

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