Is CLEC9A p.Pro112Arg (c.335C>G) pathogenic?

CLEC9A p.Pro112Arg (c.335C>G) is classified Uncertain significance in CLEC9A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.1306); Ultra-rare (popmax 0.0764%, eas).

How common is CLEC9A p.Pro112Arg (c.335C>G) in the general population?

CLEC9A p.Pro112Arg (c.335C>G) is ultra-rare (popmax 0.0764%, eas) (gnomAD).

What do computational predictors say about CLEC9A p.Pro112Arg (c.335C>G)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

CLEC9A p.Pro112Arg

c.335C>G · rs750399179 · VCV2368955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0764%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP 1.5, phastCons 0.25
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.074 · regional, not allelic
Overall
CADD	21.2	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 0.0764% East Asian · 34/44,474 alleles

Filtering AF 0.0562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0492%

Overall 0.00218% 35/1,603,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0764%	1,308
Remaining individualsnot grpmax-eligible	0.00161%	62,008

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: CLEC9A
Protein: p.Pro112Arg
Coding: c.335C>G
MANE Select: NM_207345
dbSNP: rs750399179
Type: single nucleotide variant
Location: chr12:10063070 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34 · 1 PDB

Full CLEC9A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC9A p.Ala16Thr Benign ★★ same type
CLEC9A p.Ala65Val Uncertain significance ★ ⚠ same type
CLEC9A p.Arg185Cys Uncertain significance ★ ⚠ same type
CLEC9A p.Arg185His Uncertain significance ★ ⚠ same type
CLEC9A p.Asp13Gly Uncertain significance ★ ⚠ same type
CLEC9A p.Gln21Arg Uncertain significance ★ ⚠ same type
CLEC9A p.Gln75His Uncertain significance ★ ⚠ same type
CLEC9A p.Gln97Leu 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/clec9a-p-pro112arg (accessed [today's date]).

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