Is DLST p.Arg6Ser (c.16C>A) pathogenic?

DLST p.Arg6Ser (c.16C>A) is classified Uncertain significance in DLST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-10). AlphaMissense: likely benign (0.1832); Ultra-rare (popmax 0.0122%, amr).

How common is DLST p.Arg6Ser (c.16C>A) in the general population?

DLST p.Arg6Ser (c.16C>A) is ultra-rare (popmax 0.0122%, amr) (gnomAD).

What do computational predictors say about DLST p.Arg6Ser (c.16C>A)?

AlphaMissense predicts likely benign (score 0.1832) — an in-silico prediction, not a clinical call.

DLST p.Arg6Ser

c.16C>A · rs544892049 · VCV2378238

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1832 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1832	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -6.69	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 4.6	GERP 0.5, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 7,336 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	23.2	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 0.0122% Admixed American · 7/57,302 alleles

Filtering AF 0.00566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.00484% 76/1,569,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0122%	8,186
Remaining individualsnot grpmax-eligible	0.00655%	15,258
European (non-Finnish)	0.00549%	18,215
African / African-American	0.00137%	73,226

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.Arg6Ser
Coding: c.16C>A
MANE Select: NM_001933
dbSNP: rs544892049
Type: single nucleotide variant
Location: chr14:74881969 (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.Arg6Gly Uncertain significance ★ ⚠ same residue
DLST p.Ala264Val Uncertain significance ★★ ⚠ same type
DLST p.Arg437Cys Uncertain significance ★★ ⚠ same type
DLST p.Arg4Gln 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-arg6ser (accessed [today's date]).

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