Is DLST p.Arg233Cys (c.697C>T) pathogenic?

DLST p.Arg233Cys (c.697C>T) is classified Uncertain significance in DLST (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-11). AlphaMissense: likely pathogenic (0.8819); Very rare (popmax 0.0011%, sas); Associated with DLST-related disorder.

What condition is associated with DLST p.Arg233Cys (c.697C>T)?

DLST p.Arg233Cys (c.697C>T) is associated with DLST-related disorder (ClinVar).

How common is DLST p.Arg233Cys (c.697C>T) in the general population?

DLST p.Arg233Cys (c.697C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DLST p.Arg233Cys (c.697C>T)?

AlphaMissense predicts likely pathogenic (score 0.8819) — an in-silico prediction, not a clinical call.

DLST p.Arg233Cys

c.697C>T · rs1402244328 · VCV3031177

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DLST-related disorder

Computational evidence

Protein change
AlphaMissense	0.8819	likely pathogenic
REVEL	0.327	indeterminate
SaProt	LLR -15.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 3,281 bp · p 1 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,808 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	0.000169%	589,995

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: DLST
Protein: p.Arg233Cys
Coding: c.697C>T
MANE Select: NM_001933
dbSNP: rs1402244328
Type: single nucleotide variant
Location: chr14:74894336 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 233: an α-helix

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

Disease context

DLST-related disorder

Similar variants

DLST p.Ile106Val Uncertain significance ★★ ⚠ same condition
DLST p.Ala171Val Uncertain significance ★ ⚠ same condition
DLST c.442+39C>G Likely benign same condition
DLST c.-10C>T Likely benign same condition
DLST c.-7C>A Likely benign same condition
DLST p.Ala264Val Uncertain significance ★★ ⚠ same type
DLST p.Arg437Cys Uncertain significance ★★ ⚠ same type
DLST p.Arg4Gln Uncertain significance ★★ ⚠ 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/dlst-p-arg233cys (accessed [today's date]).

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