Is DPYSL2 p.Gln196= (c.588A>G) pathogenic?

DPYSL2 p.Gln196= (c.588A>G) is classified Likely benign in DPYSL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0834%, sas).

How common is DPYSL2 p.Gln196= (c.588A>G) in the general population?

DPYSL2 p.Gln196= (c.588A>G) is ultra-rare (popmax 0.0834%, sas) (gnomAD).

DPYSL2 p.Gln196=

c.588A>G · rs753474956 · VCV2658495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0834%, sas)

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 3	GERP -1, phastCons 1
Overall
CADD	9.875	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0834% South Asian · 76/91,080 alleles

Filtering AF 0.0683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0628%

Overall 0.00477% 77/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0834%	1,198
European (non-Finnish)	8.47e-05%	1,180,048

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: DPYSL2
Protein: p.Gln196=
Coding: c.588A>G
MANE Select: NM_001197293
dbSNP: rs753474956
Type: single nucleotide variant
Location: chr8:26583943 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 15 PDB
Residue 196: a β-strand

Full DPYSL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRP2 p.Asn196Lys Uncertain significance ★ ⚠ same residue
DRP2 p.Glu432Ter Pathogenic ★★ same type
DPYSL2 p.Asn492Ser Uncertain significance ★★ ⚠ same type
DPYSL2 p.Asp520Asn Uncertain significance ★★ ⚠ same type
DRP2 p.Ala205Val Uncertain significance ★★ ⚠ same type
DRP2 p.Ala643Thr Uncertain significance ★★ ⚠ same type
DRP2 p.Arg199His Uncertain significance ★★ ⚠ same type
DRP2 p.Arg224Cys 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/dpysl2-p-gln196 (accessed [today's date]).

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