Is DST p.Pro1355= (c.4065T>C) pathogenic?

DST p.Pro1355= (c.4065T>C) is classified Likely benign in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-11). Very rare (popmax 0.00127%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DST p.Pro1355= (c.4065T>C)?

DST p.Pro1355= (c.4065T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DST p.Pro1355= (c.4065T>C) in the general population?

DST p.Pro1355= (c.4065T>C) is very rare (popmax 0.00127%, nfe) (gnomAD).

DST p.Pro1355=

c.4065T>C · rs2536971666 · VCV1736561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -4.7
Overall
CADD	0.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,884 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00103% 15/1,461,684 alleles · very rare

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.Pro1355=
Coding: c.4065T>C
MANE Select: NM_001374736
dbSNP: rs2536971666
Type: single nucleotide variant
Location: chr6:56631288 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)

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.Pro1355Arg Uncertain significance ★★ same residue
DST p.Glu1355Gln Uncertain significance ★ same residue
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

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-pro1355 (accessed [today's date]).

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