Is DGCR2 p.Pro116Ala (c.346C>G) pathogenic?

DGCR2 p.Pro116Ala (c.346C>G) is classified Uncertain significance in DGCR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: ambiguous (0.5442); Very rare (popmax 0.00737%, nfe).

How common is DGCR2 p.Pro116Ala (c.346C>G) in the general population?

DGCR2 p.Pro116Ala (c.346C>G) is very rare (popmax 0.00737%, nfe) (gnomAD).

What do computational predictors say about DGCR2 p.Pro116Ala (c.346C>G)?

AlphaMissense predicts ambiguous (score 0.5442) — an in-silico prediction, not a clinical call.

DGCR2 p.Pro116Ala

c.346C>G · VCV4659697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5442 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5442	ambiguous
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -9.16	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 65 kb · p 0.014 · regional, not allelic
Overall
CADD	27.8	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 0.00737% European (non-Finnish) · 87/1,180,004 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00539% 87/1,613,760 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: DGCR2
Protein: p.Pro116Ala
Coding: c.346C>G
MANE Select: NM_005137
Type: single nucleotide variant
Location: chr22:19065050 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.74
Residue 116: the c-type lectin domain

Full DGCR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DGCR2 p.Pro116Leu Uncertain significance ★ ⚠ same residue
DGCR2 p.Arg74His Uncertain significance ★★ ⚠ same type
DGCR2 p.Val102Met Uncertain significance ★★ ⚠ same type
DGCR2 p.Ala141= Benign ★★ same type
DGCR2 p.Leu11= Benign/Likely benign ★★ same type
DGCR2 p.Pro439= Benign/Likely benign ★★ same type
DGCR2 p.Ala142Glu Uncertain significance ★ ⚠ same type
DGCR2 p.Ala153Thr 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/dgcr2-p-pro116ala (accessed [today's date]).

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