Is DRG2 p.Arg310Trp (c.928C>T) pathogenic?

DRG2 p.Arg310Trp (c.928C>T) is classified Uncertain significance in DRG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.8369); Very rare (popmax 0.00167%, amr).

How common is DRG2 p.Arg310Trp (c.928C>T) in the general population?

DRG2 p.Arg310Trp (c.928C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DRG2 p.Arg310Trp (c.928C>T)?

AlphaMissense predicts likely pathogenic (score 0.8369) — an in-silico prediction, not a clinical call.

DRG2 p.Arg310Trp

c.928C>T · VCV4014860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8369	likely pathogenic
REVEL	0.477	indeterminate
SaProt	LLR -14.65	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 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.2e-10 · regional, not allelic
Overall
CADD	34.0	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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,613,758 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00314%	31,857
Admixed Americangrpmax	0.00167%	59,998
European (non-Finnish)	0.000339%	295,011

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg310Trp
Coding: c.928C>T
MANE Select: NM_001388
Type: single nucleotide variant
Location: chr17:18104655 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40
Residue 310: the tgs 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.Ala63Val 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-arg310trp (accessed [today's date]).

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