Is DST c.18357+84C>T pathogenic?

DST c.18357+84C>T is classified Benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-06). Common (popmax 70.7%, nfe) — too common for a highly-penetrant pathogenic allele.

DST c.18357+84C>T

Q: How common is DST c.18357+84C>T in the general population?

DST c.18357+84C>T is common (popmax 70.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4715626 · VCV1288855

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 70.7%, nfe) — 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
Splice region	donor +84	deep intronic (+84 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -0.81, phastCons 0.002
Non-coding constraint	Z 1.17	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	0.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.7% European (non-Finnish) · 424,717/600,878 alleles

Filtering AF 70.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.4%

Overall 69.3% 665,100/960,358 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	81.2%	1
European (non-Finnish)grpmax	70.7%	1
Admixed American	70.2%	1
East Asian	67.2%	1
Remaining individualsnot grpmax-eligible	66.9%	1
South Asian	66.1%	2
Middle Eastern	61.6%	2
Ashkenazi Jewishnot grpmax-eligible	57%	2
Amishnot grpmax-eligible	56.1%	2
African / African-American	54.7%	2

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: DST
Coding: c.18357+84C>T
MANE Select: NM_001374736
dbSNP: rs4715626
Type: single nucleotide variant
Location: chr6:56517114 (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

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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
DST p.Gln1366Ter 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-c-18357-plus-84c-t (accessed [today's date]).

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