Is DLST p.Arg413Gln (c.1238G>A) pathogenic?

DLST p.Arg413Gln (c.1238G>A) is classified Uncertain significance in DLST (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: ambiguous (0.4213); Very rare (popmax 0.000598%, nfe).

How common is DLST p.Arg413Gln (c.1238G>A) in the general population?

DLST p.Arg413Gln (c.1238G>A) is very rare (popmax 0.000598%, nfe) (gnomAD).

What do computational predictors say about DLST p.Arg413Gln (c.1238G>A)?

AlphaMissense predicts ambiguous (score 0.4213) — an in-silico prediction, not a clinical call.

DLST p.Arg413Gln

c.1238G>A · rs767072522 · VCV2258450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000598%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4213	ambiguous
REVEL	0.482	indeterminate
SaProt	LLR -14.96	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,926 bp · p 4e-06 · regional, not allelic
Overall
CADD	33.0	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 0.000598% European (non-Finnish) · 7/1,170,522 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000484% 7/1,445,854 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: DLST
Protein: p.Arg413Gln
Coding: c.1238G>A
MANE Select: NM_001933
dbSNP: rs767072522
Type: single nucleotide variant
Location: chr14:74902206 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 413: a β-strand

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

Similar variants

DLST p.Ala264Val Uncertain significance ★★ ⚠ same type
DLST p.Arg437Cys Uncertain significance ★★ ⚠ same type
DLST p.Arg4Gln Uncertain significance ★★ ⚠ same type
DLST p.Arg6Ser Uncertain significance ★★ ⚠ same type
DLST p.Asn44Ser Uncertain significance ★★ ⚠ same type
DLST p.Asn51Asp Uncertain significance ★★ ⚠ same type
DLST p.Asp304Gly Uncertain significance ★★ ⚠ same type
DLST p.Gly216Val 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-arg413gln (accessed [today's date]).

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