Is DRG2 p.Val193Ile (c.577G>A) pathogenic?

DRG2 p.Val193Ile (c.577G>A) is classified Benign in DRG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-10). AlphaMissense: likely benign (0.0964); Rare (popmax 0.464%, nfe).

How common is DRG2 p.Val193Ile (c.577G>A) in the general population?

DRG2 p.Val193Ile (c.577G>A) is rare (popmax 0.464%, nfe) (gnomAD).

What do computational predictors say about DRG2 p.Val193Ile (c.577G>A)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

DRG2 p.Val193Ile

c.577G>A · rs143296623 · VCV782152

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.464%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 19 kb · p 2.2e-10 · regional, not allelic
Overall
CADD	23.2	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 0.464% European (non-Finnish) · 5,477/1,180,034 alleles

Filtering AF 0.454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.45%

Overall 0.437% 7,058/1,614,174 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.78%	56
European (non-Finnish)grpmax	0.464%	215
Remaining individualsnot grpmax-eligible	0.37%	271
Middle Eastern	0.198%	505
Admixed American	0.155%	645
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0946%	1,057
South Asian	0.0395%	2,530

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.Val193Ile
Coding: c.577G>A
MANE Select: NM_001388
dbSNP: rs143296623
Type: single nucleotide variant
Location: chr17:18100605 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40
Residue 193: 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.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-val193ile (accessed [today's date]).

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