Is DLAT p.Pro401Leu (c.1202C>T) pathogenic?

DLAT p.Pro401Leu (c.1202C>T) is classified Uncertain significance in DLAT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-28). AlphaMissense: likely benign (0.0714); Very rare (popmax 0.00988%, sas); Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Pro401Leu (c.1202C>T)?

DLAT p.Pro401Leu (c.1202C>T) is associated with Inborn genetic diseases, pyruvate dehydrogenase E2 deficiency (ClinVar).

How common is DLAT p.Pro401Leu (c.1202C>T) in the general population?

DLAT p.Pro401Leu (c.1202C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about DLAT p.Pro401Leu (c.1202C>T)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

DLAT p.Pro401Leu

c.1202C>T · rs781794850 · VCV547881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 0.92
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	23.8	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 0.00988% South Asian · 9/91,080 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00242% 39/1,613,738 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,120
Remaining individualsnot grpmax-eligible	0.0048%	20,821
African / African-American	0.00267%	37,442
European (non-Finnish)	0.00203%	49,161
Admixed American	0.00167%	59,990

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.Pro401Leu
Coding: c.1202C>T
MANE Select: NM_001931
dbSNP: rs781794850
Type: single nucleotide variant
Location: chr11:112045142 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB

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

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-pro401leu (accessed [today's date]).

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