Is DST p.Arg92Cys (c.274C>T) pathogenic?

DST p.Arg92Cys (c.274C>T) is classified Uncertain significance in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). Very rare (popmax 0.00264%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DST p.Arg92Cys (c.274C>T)?

DST p.Arg92Cys (c.274C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DST p.Arg92Cys (c.274C>T) in the general population?

DST p.Arg92Cys (c.274C>T) is very rare (popmax 0.00264%, nfe) (gnomAD).

DST p.Arg92Cys

c.274C>T · rs748769120 · VCV1795534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00264%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.467	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00264% European (non-Finnish) · 27/1,021,846 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00155%

Overall 0.00219% 30/1,367,460 alleles · very rare exomes 27/1,215,382 · genomes 3/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00264%	37,846
Remaining individualsnot grpmax-eligible	0.00217%	46,094
Admixed American	0.0019%	52,540
African / African-American	0.00148%	67,698

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.Arg92Cys
Coding: c.274C>T
MANE Select: NM_001374736
dbSNP: rs748769120
Type: single nucleotide variant
Location: chr6:56900564 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Residue 92: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DST p.Gln4023Ter Pathogenic/Likely pathogenic ★★ same condition
DST c.16770+5T>C Uncertain significance ★★ same condition
DST c.17269-3T>A Uncertain significance ★★ same condition
DST c.18129+3A>G Uncertain significance ★★ same condition
DST c.182-5C>T Uncertain significance ★★ same condition
DST c.19896+4C>T Uncertain significance ★★ same condition
DST c.20551-3A>C Uncertain significance ★★ same condition
DST c.22959+3A>G Uncertain significance ★★ same condition

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-arg92cys (accessed [today's date]).

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