Is DST p.Phe35Cys (c.104T>G) pathogenic?

DST p.Phe35Cys (c.104T>G) is classified Uncertain significance in DST (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-27). Ultra-rare (popmax 0.0386%, sas); Associated with Inborn genetic diseases.

What condition is associated with DST p.Phe35Cys (c.104T>G)?

DST p.Phe35Cys (c.104T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DST p.Phe35Cys (c.104T>G) in the general population?

DST p.Phe35Cys (c.104T>G) is ultra-rare (popmax 0.0386%, sas) (gnomAD).

DST p.Phe35Cys

c.104T>G · rs369858396 · VCV1776742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.608	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.025, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 320 kb · p 2.5e-12 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% South Asian · 34/88,022 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0248%

Overall 0.00402% 55/1,367,550 alleles · ultra-rare exomes 48/1,215,260 · genomes 7/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0386%	2,589
East Asian	0.0319%	3,135
Remaining individualsnot grpmax-eligible	0.00651%	15,371
European (non-Finnish)	0.00108%	92,892

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.Phe35Cys
Coding: c.104T>G
MANE Select: NM_001374736
dbSNP: rs369858396
Type: single nucleotide variant
Location: chr6:56954484 (GRCh38)
Gene constraint: LOEUF 0.297 · pLI 1.00 (gnomAD)
Residue 35: 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.Phe35del Uncertain significance ★ same residue
DST p.His35Arg Uncertain significance ★ same residue
DST p.His35Leu 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

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-phe35cys (accessed [today's date]).

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