Is DLST p.Arg4Gly (c.10C>G) pathogenic?

DLST p.Arg4Gly (c.10C>G) is classified Uncertain significance in DLST (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.0917); Ultra-rare (popmax 0.0384%, afr).

How common is DLST p.Arg4Gly (c.10C>G) in the general population?

DLST p.Arg4Gly (c.10C>G) is ultra-rare (popmax 0.0384%, afr) (gnomAD).

What do computational predictors say about DLST p.Arg4Gly (c.10C>G)?

AlphaMissense predicts likely benign (score 0.0917) — an in-silico prediction, not a clinical call.

DLST p.Arg4Gly

c.10C>G · VCV3502464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0917 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0917	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.99	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 3.1	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	21.6	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 0.0384% African / African-American · 28/72,944 alleles

Filtering AF 0.0272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.00364% 57/1,566,574 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0384%	2,605
Middle Eastern	0.0346%	2,891
South Asian	0.0023%	43,406
European (non-Finnish)	0.00198%	50,612
Admixed American	0.00176%	56,900
Remaining individualsnot grpmax-eligible	0.00164%	60,876

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.Arg4Gly
Coding: c.10C>G
MANE Select: NM_001933
Type: single nucleotide variant
Location: chr14:74881963 (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.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-arg4gly (accessed [today's date]).

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