Is DLST p.Ser288Leu (c.863C>T) pathogenic?

DLST p.Ser288Leu (c.863C>T) is classified Uncertain significance in DLST (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.5156); Very rare (popmax 0.00668%, eas).

How common is DLST p.Ser288Leu (c.863C>T) in the general population?

DLST p.Ser288Leu (c.863C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about DLST p.Ser288Leu (c.863C>T)?

AlphaMissense predicts ambiguous (score 0.5156) — an in-silico prediction, not a clinical call.

DLST p.Ser288Leu

c.863C>T · rs763725822 · VCV2482605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5156	ambiguous
REVEL	0.159	moderately benign-leaning
SaProt	LLR -12.98	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.77, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 7,926 bp · p 4e-06 · regional, not allelic
Overall
CADD	25.2	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 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000274% 4/1,461,796 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
European (non-Finnish)	8.47e-05%	1,180,034

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: DLST
Protein: p.Ser288Leu
Coding: c.863C>T
MANE Select: NM_001933
dbSNP: rs763725822
Type: single nucleotide variant
Location: chr14:74898461 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 288: an α-helix

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

Similar variants

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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-ser288leu (accessed [today's date]).

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