Is CLEC16A p.Gln205Pro (c.614A>C) pathogenic?

CLEC16A p.Gln205Pro (c.614A>C) is classified Uncertain significance in CLEC16A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1263); Very rare (popmax 0.00274%, afr).

How common is CLEC16A p.Gln205Pro (c.614A>C) in the general population?

CLEC16A p.Gln205Pro (c.614A>C) is very rare (popmax 0.00274%, afr) (gnomAD).

What do computational predictors say about CLEC16A p.Gln205Pro (c.614A>C)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

CLEC16A p.Gln205Pro

c.614A>C · rs1434028977 · VCV2255124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 17 kb · p 8.6e-11 · regional, not allelic
Overall
CADD	25.8	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 0.00274% African / African-American · 2/73,112 alleles

Filtering AF 0.000454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000125% 2/1,601,474 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.Gln205Pro
Coding: c.614A>C
MANE Select: NM_015226
dbSNP: rs1434028977
Type: single nucleotide variant
Location: chr16:10972947 (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.Gln205Glu 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-gln205pro (accessed [today's date]).

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