Is DLAT p.Ser593Ala (c.1777T>G) pathogenic?

DLAT p.Ser593Ala (c.1777T>G) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely benign (0.0962); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Ser593Ala (c.1777T>G)?

DLAT p.Ser593Ala (c.1777T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DLAT p.Ser593Ala (c.1777T>G) in the general population?

DLAT p.Ser593Ala (c.1777T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLAT p.Ser593Ala (c.1777T>G)?

AlphaMissense predicts likely benign (score 0.0962) — an in-silico prediction, not a clinical call.

DLAT p.Ser593Ala

c.1777T>G · VCV3502235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0962 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0962	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -5.94	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 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLAT
Protein: p.Ser593Ala
Coding: c.1777T>G
MANE Select: NM_001931
Type: single nucleotide variant
Location: chr11:112061137 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 593: a β-strand

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

Similar variants

DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT p.Ala253Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg429Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg430Gln Uncertain significance ★★ ⚠ same condition
DLAT p.Arg56Pro Uncertain significance ★★ ⚠ same condition
DLAT p.Arg70Trp Uncertain significance ★★ ⚠ same condition
DLAT p.Asp390Asn Uncertain significance ★★ ⚠ same condition
DLAT p.Glu469Gly 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-ser593ala (accessed [today's date]).

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