Is DLAT p.Glu115fs (c.342del) pathogenic?

DLAT p.Glu115fs (c.342del) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Very rare (popmax 0.00136%, afr).

How common is DLAT p.Glu115fs (c.342del) in the general population?

DLAT p.Glu115fs (c.342del) is very rare (popmax 0.00136%, afr) (gnomAD).

DLAT p.Glu115fs

c.342del · VCV4821252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,434 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00025% 4/1,600,778 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00161%	62,196
African / African-Americangrpmax	0.00136%	73,434
European (non-Finnish)	0.00017%	587,289

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DLAT
Protein: p.Glu115fs
Coding: c.342del
MANE Select: NM_001931
Type: Deletion
Location: chr11:112026253 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 115: the lipoyl-binding 1 domain

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

Similar variants

DLAT p.Glu115del Uncertain significance ★ same residue
DLAT p.Glu115Lys Uncertain significance ★ ⚠ same residue
DLAT p.Asp283fs Pathogenic/Likely pathogenic ★★ same type
DLAT p.Thr322_Pro325del Uncertain significance ★★ same type
DLAT c.381+22delT Benign/Likely benign ★★ same type
DLAT p.Cys344fs Likely pathogenic ★ same type
DLAT p.Glu268fs Pathogenic ★ same type
DLAT p.Ile159fs Likely pathogenic ★ 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/dlat-p-glu115fs (accessed [today's date]).

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