Is DLST p.Arg4= (c.12A>G) pathogenic?

DLST p.Arg4= (c.12A>G) is classified Likely benign in DLST (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0252%, nfe).

How common is DLST p.Arg4= (c.12A>G) in the general population?

DLST p.Arg4= (c.12A>G) is ultra-rare (popmax 0.0252%, nfe) (gnomAD).

DLST p.Arg4=

c.12A>G · rs373129809 · VCV2714996

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0252%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -3.1, phastCons 1
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0252% European (non-Finnish) · 292/1,160,218 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.0212% 330/1,558,652 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0252%	3,973
Admixed American	0.025%	4,008
Remaining individualsnot grpmax-eligible	0.0248%	4,027
African / African-American	0.0097%	10,309
Finnishnot grpmax-eligible	0.00417%	23,964

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.Arg4=
Coding: c.12A>G
MANE Select: NM_001933
dbSNP: rs373129809
Type: single nucleotide variant
Location: chr14:74881965 (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.Arg4Gln Uncertain significance ★★ ⚠ same residue
DLST p.Arg4Gly Uncertain significance ★ ⚠ 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-arg4 (accessed [today's date]).

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