Is DST p.Arg75Lys (c.224G>A) pathogenic?

DST p.Arg75Lys (c.224G>A) is classified Likely benign in DST (ClinVar, Single submitter, 3 submitters; last evaluated 2021-01-08). Rare (popmax 0.363%, sas); Associated with Inborn genetic diseases.

What condition is associated with DST p.Arg75Lys (c.224G>A)?

DST p.Arg75Lys (c.224G>A) is associated with Inborn genetic diseases, epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (ClinVar).

How common is DST p.Arg75Lys (c.224G>A) in the general population?

DST p.Arg75Lys (c.224G>A) is rare (popmax 0.363%, sas) (gnomAD).

DST p.Arg75Lys

c.224G>A · rs563479643 · VCV1050714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.363%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.34	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% South Asian · 320/88,038 alleles

Filtering AF 0.331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.318%

Overall 0.0242% 331/1,367,500 alleles · rare exomes 309/1,215,180 · genomes 22/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.363%	275
Remaining individualsnot grpmax-eligible	0.0195%	5,123
Admixed American	0.0019%	52,570
European (non-Finnish)	9.79e-05%	1,021,792

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.Arg75Lys
Coding: c.224G>A
MANE Select: NM_001374736
dbSNP: rs563479643
Type: single nucleotide variant
Location: chr6:56900614 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Residue 75: 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

Also linked: epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Similar variants

DST c.22959+1G>A Likely pathogenic ★★ same condition
DST p.Arg1512Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg1696Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Arg7329Ter Pathogenic ★★ same condition
DST p.Cys1828Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Gln1124Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Gln1366Ter Pathogenic/Likely pathogenic ★★ same condition
DST p.Gln1665Ter Pathogenic ★★ 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-arg75lys (accessed [today's date]).

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