Is DST p.Arg7739Ter (c.23215C>T) pathogenic?

DST p.Arg7739Ter (c.23215C>T) is classified Uncertain significance in DST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-05). Very rare (popmax 0.0011%, sas).

How common is DST p.Arg7739Ter (c.23215C>T) in the general population?

DST p.Arg7739Ter (c.23215C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

DST p.Arg7739Ter

c.23215C>T · rs1270744282 · VCV1162987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (104 of 104) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.58, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,774 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,400 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,774
European (non-Finnish)	0.000254%	393,071

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: DST
Protein: p.Arg7739Ter
Coding: c.23215C>T
MANE Select: NM_001374736
dbSNP: rs1270744282
Type: single nucleotide variant
Location: chr6:56459247 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)

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

Similar variants

DST p.Arg7739Gln Uncertain significance ★ same residue
DST c.22959+1G>A Likely pathogenic ★★ same type
DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same type
DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same type
DST p.Arg22Ter Likely pathogenic ★★ same type
DST p.Arg7329Ter Pathogenic ★★ same type
DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same type
DST p.Gln1124Ter Pathogenic/Likely pathogenic ★★ 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/dst-p-arg7739ter (accessed [today's date]).

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