Is CLEC16A p.Arg212Pro (c.635G>C) pathogenic?

CLEC16A p.Arg212Pro (c.635G>C) is classified Uncertain significance in CLEC16A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is CLEC16A p.Arg212Pro (c.635G>C) in the general population?

CLEC16A p.Arg212Pro (c.635G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLEC16A p.Arg212Pro (c.635G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CLEC16A p.Arg212Pro

c.635G>C · VCV4229682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 3% in CLEC16A
REVEL	0.607	indeterminate
SaProt	LLR -16.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 17 kb · p 8.6e-11 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLEC16A
Protein: p.Arg212Pro
Coding: c.635G>C
MANE Select: NM_015226
Type: single nucleotide variant
Location: chr16:10972968 (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-arg212pro (accessed [today's date]).

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