Is DLST p.Arg345Trp (c.1033C>T) pathogenic?

DLST p.Arg345Trp (c.1033C>T) is classified Uncertain significance in DLST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1876); Very rare (popmax 0.00439%, sas).

How common is DLST p.Arg345Trp (c.1033C>T) in the general population?

DLST p.Arg345Trp (c.1033C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about DLST p.Arg345Trp (c.1033C>T)?

AlphaMissense predicts likely benign (score 0.1876) — an in-silico prediction, not a clinical call.

DLST p.Arg345Trp

c.1033C>T · rs529335333 · VCV2364987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1876	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -14.80	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,926 bp · p 4e-06 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,064 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.0026% 42/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,766
Admixed American	0.00333%	30,010
European (non-Finnish)	0.00297%	33,710
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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.Arg345Trp
Coding: c.1033C>T
MANE Select: NM_001933
dbSNP: rs529335333
Type: single nucleotide variant
Location: chr14:74900346 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 345: an α-helix

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

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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-arg345trp (accessed [today's date]).

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