Is DLST p.Pro139Leu (c.416C>T) pathogenic?

DLST p.Pro139Leu (c.416C>T) is classified Uncertain significance in DLST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.1648); Absent from gnomAD v4.1.

How common is DLST p.Pro139Leu (c.416C>T) in the general population?

DLST p.Pro139Leu (c.416C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLST p.Pro139Leu (c.416C>T)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

DLST p.Pro139Leu

c.416C>T · VCV4241235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -11.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 3,281 bp · p 1 · regional, not allelic
Overall
CADD	25.9	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

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: DLST
Protein: p.Pro139Leu
Coding: c.416C>T
MANE Select: NM_001933
Type: single nucleotide variant
Location: chr14:74891141 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 139: the lipoyl-binding domain

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

Similar variants

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DLST p.Arg437Cys Uncertain significance ★★ ⚠ same type
DLST p.Arg4Gln Uncertain significance ★★ ⚠ same type
DLST p.Arg6Ser 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-pro139leu (accessed [today's date]).

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