Is DRG2 p.Ala63Val (c.188C>T) pathogenic?

DRG2 p.Ala63Val (c.188C>T) is classified Uncertain significance in DRG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely pathogenic (0.9164); Very rare (popmax 0.00347%, nfe).

How common is DRG2 p.Ala63Val (c.188C>T) in the general population?

DRG2 p.Ala63Val (c.188C>T) is very rare (popmax 0.00347%, nfe) (gnomAD).

What do computational predictors say about DRG2 p.Ala63Val (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.9164) — an in-silico prediction, not a clinical call.

DRG2 p.Ala63Val

c.188C>T · VCV3842480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00347%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9164	likely pathogenic
REVEL	0.515	indeterminate
SaProt	LLR -13.44	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 7.7	GERP 0.77, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.2e-10 · regional, not allelic
Overall
CADD	29.8	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

Grpmax group 0.00347% European (non-Finnish) · 41/1,180,046 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.0026% 42/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00347%	28,782
African / African-American	0.00133%	74,932

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: DRG2
Protein: p.Ala63Val
Coding: c.188C>T
MANE Select: NM_001388
Type: single nucleotide variant
Location: chr17:18093936 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40
Residue 63: the obg-type g domain

Full DRG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRG2 p.Ile359= Benign ★★ same type
DRG2 p.Ala135Ser Uncertain significance ★ ⚠ same type
DRG2 p.Ala137Val Uncertain significance ★ ⚠ same type
DRG2 p.Ala260Val Uncertain significance ★ ⚠ same type
DRG2 p.Ala306Thr Uncertain significance ★ ⚠ same type
DRG2 p.Ala32Val Uncertain significance ★ ⚠ same type
DRG2 p.Ala35Thr Uncertain significance ★ ⚠ same type
DRG2 p.Ala86Thr 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/drg2-p-ala63val (accessed [today's date]).

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