Is DLAT p.Ile579Val (c.1735A>G) pathogenic?

DLAT p.Ile579Val (c.1735A>G) is classified Conflicting classifications of pathogenicity in DLAT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.2015); Ultra-rare (popmax 0.0334%, eas); Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Ile579Val (c.1735A>G)?

DLAT p.Ile579Val (c.1735A>G) is associated with Inborn genetic diseases, pyruvate dehydrogenase E2 deficiency, Leigh syndrome (ClinVar).

How common is DLAT p.Ile579Val (c.1735A>G) in the general population?

DLAT p.Ile579Val (c.1735A>G) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

What do computational predictors say about DLAT p.Ile579Val (c.1735A>G)?

AlphaMissense predicts likely benign (score 0.2015) — an in-silico prediction, not a clinical call.

DLAT p.Ile579Val

c.1735A>G · rs371341957 · VCV1661511

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2015	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -5.84	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,874 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00452% 73/1,613,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,345
East Asiangrpmax	0.0334%	2,992
South Asian	0.0033%	30,342
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.00263%	38,059

Ashkenazi Jewish 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.Ile579Val
Coding: c.1735A>G
MANE Select: NM_001931
dbSNP: rs371341957
Type: single nucleotide variant
Location: chr11:112061095 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 579: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pyruvate dehydrogenase E2 deficiency Leigh syndrome

Similar variants

DLAT c.976-1G>A Pathogenic/Likely pathogenic ★★ same condition
DLAT p.Arg435Ter Pathogenic ★★ same condition
DLAT p.Glu138Ter Pathogenic ★★ same condition
DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT c.1130-6T>G Uncertain significance ★★ same condition
DLAT p.Ala109Thr Uncertain significance ★★ ⚠ same condition
DLAT p.Ala191Gly Uncertain significance ★★ ⚠ same condition
DLAT p.Ala191Val Uncertain significance ★★ ⚠ same condition

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-ile579val (accessed [today's date]).

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