Is DGCR2 p.Ala99Val (c.296C>T) pathogenic?

DGCR2 p.Ala99Val (c.296C>T) is classified Uncertain significance in DGCR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0119%, amr).

How common is DGCR2 p.Ala99Val (c.296C>T) in the general population?

DGCR2 p.Ala99Val (c.296C>T) is ultra-rare (popmax 0.0119%, amr) (gnomAD).

What do computational predictors say about DGCR2 p.Ala99Val (c.296C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

DGCR2 p.Ala99Val

c.296C>T · VCV4239778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.3	GERP 1.8, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 65 kb · p 0.014 · regional, not allelic
Overall
CADD	17.19	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 0.0119% Admixed American · 7/59,026 alleles

Filtering AF 0.00551% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00386%

Overall 0.0023% 37/1,607,466 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0119%	8,432
African / African-American	0.00401%	24,923
European (non-Finnish)	0.00221%	45,307
Remaining individualsnot grpmax-eligible	0.00161%	62,252

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.Ala99Val
Coding: c.296C>T
MANE Select: NM_005137
Type: single nucleotide variant
Location: chr22:19068132 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.74

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

Similar variants

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
DGCR2 p.Ala469Gly 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-ala99val (accessed [today's date]).

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