Is DRG2 p.Ile359= (c.1077C>T) pathogenic?

DRG2 p.Ile359= (c.1077C>T) is classified Benign in DRG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-26). Common (popmax 9.72%, afr) — too common for a highly-penetrant pathogenic allele.

DRG2 p.Ile359=

Q: How common is DRG2 p.Ile359= (c.1077C>T) in the general population?

DRG2 p.Ile359= (c.1077C>T) is common (popmax 9.72%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1077C>T · rs2230317 · VCV768839

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.72%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.37, phastCons 1
Overall
CADD	9.831	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.72% African / African-American · 7,296/75,024 alleles

Filtering AF 9.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.46%

Overall 0.526% 8,486/1,613,272 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.72%	10
Remaining individualsnot grpmax-eligible	0.744%	134
Admixed American	0.74%	135
Middle Eastern	0.412%	242
Ashkenazi Jewishnot grpmax-eligible	0.176%	569
South Asian	0.0428%	2,335
European (non-Finnish)	0.0139%	7,195
East Asian	0.00223%	44,890

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.Ile359=
Coding: c.1077C>T
MANE Select: NM_001388
dbSNP: rs2230317
Type: single nucleotide variant
Location: chr17:18107222 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40
Residue 359: the tgs domain

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

Similar variants

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
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-ile359 (accessed [today's date]).

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