Is DLST p.Pro204Leu (c.611C>T) pathogenic?

DLST p.Pro204Leu (c.611C>T) is classified Benign in DLST (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1491); Low-frequency (popmax 2.95%, mid).

How common is DLST p.Pro204Leu (c.611C>T) in the general population?

DLST p.Pro204Leu (c.611C>T) is low-frequency (popmax 2.95%, mid) (gnomAD).

What do computational predictors say about DLST p.Pro204Leu (c.611C>T)?

AlphaMissense predicts likely benign (score 0.1491) — an in-silico prediction, not a clinical call.

DLST p.Pro204Leu

c.611C>T · rs142872233 · VCV2843141

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1491 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.95%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1491	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 3,281 bp · p 1 · regional, not allelic
Overall
CADD	21.1	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 2.95% Middle Eastern · 179/6,062 alleles

Filtering AF 2.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.46%

Overall 1.89% 30,499/1,614,178 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.01%	33
Middle Easterngrpmax	2.95%	34
European (non-Finnish)	2.12%	47
Remaining individualsnot grpmax-eligible	1.91%	52
Admixed American	1.63%	61
Ashkenazi Jewishnot grpmax-eligible	1.54%	65
South Asian	0.516%	194
African / African-American	0.393%	254
Amishnot grpmax-eligible	0.11%	912
East Asian	0.0111%	8,978

Finnish 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: DLST
Protein: p.Pro204Leu
Coding: c.611C>T
MANE Select: NM_001933
dbSNP: rs142872233
Type: single nucleotide variant
Location: chr14:74893363 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB
Residue 204: the 'disordered' region

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-pro204leu (accessed [today's date]).

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