Is DLST p.Arg4Gln (c.11G>A) pathogenic?

DLST p.Arg4Gln (c.11G>A) is classified Uncertain significance in DLST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). AlphaMissense: likely benign (0.1164); Ultra-rare (popmax 0.0519%, mid).

How common is DLST p.Arg4Gln (c.11G>A) in the general population?

DLST p.Arg4Gln (c.11G>A) is ultra-rare (popmax 0.0519%, mid) (gnomAD).

What do computational predictors say about DLST p.Arg4Gln (c.11G>A)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

DLST p.Arg4Gln

c.11G>A · rs774943636 · VCV2644373

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0519%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 7,336 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0519% Middle Eastern · 3/5,784 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.011% 172/1,566,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0519%	1,928
European (non-Finnish)	0.0131%	7,609
Remaining individualsnot grpmax-eligible	0.00821%	12,175
Ashkenazi Jewishnot grpmax-eligible	0.00693%	14,437
South Asian	0.00691%	14,480
Admixed American	0.00351%	28,477
African / African-American	0.00137%	72,918

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.Arg4Gln
Coding: c.11G>A
MANE Select: NM_001933
dbSNP: rs774943636
Type: single nucleotide variant
Location: chr14:74881964 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB

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

Similar variants

DLST p.Arg4Gly Uncertain significance ★ ⚠ same residue
DLST p.Arg4= Likely benign ★ same residue
DLST p.Ala264Val Uncertain significance ★★ ⚠ same type
DLST p.Arg437Cys 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

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-arg4gln (accessed [today's date]).

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