Is DST c.21675+162C>A pathogenic?

DST c.21675+162C>A is classified Benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-08). Common (popmax 43.5%, mid) — too common for a highly-penetrant pathogenic allele.

DST c.21675+162C>A

Q: How common is DST c.21675+162C>A in the general population?

DST c.21675+162C>A is common (popmax 43.5%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2273973 · VCV1241343

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 43.5%, mid) — 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 +162	deep intronic (+162 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -3.6
Non-coding constraint	Z 2.64	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	1.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.5% Middle Eastern · 128/294 alleles

Filtering AF 37.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.1%

Overall 31.9% 48,493/151,982 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	44.1%	2
Ashkenazi Jewishnot grpmax-eligible	44%	2
Middle Easterngrpmax	43.5%	2
Remaining individualsnot grpmax-eligible	36.3%	3
African / African-American	34.9%	3
Admixed American	33.4%	3
South Asian	33.2%	3
European (non-Finnish)	31.4%	3
East Asian	22.4%	4
Finnishnot grpmax-eligible	19.1%	5

Amish 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.21675+162C>A
MANE Select: NM_001374736
dbSNP: rs2273973
Type: single nucleotide variant
Location: chr6:56477183 (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 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
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-21675-plus-162c-a (accessed [today's date]).

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