Is DLST p.Val49Ile (c.145G>A) pathogenic?

DLST p.Val49Ile (c.145G>A) is classified Likely benign in DLST (ClinVar, Single submitter, 3 submitters; last evaluated 2025-01-20). AlphaMissense: likely benign (0.0697); Rare (popmax 0.369%, sas).

How common is DLST p.Val49Ile (c.145G>A) in the general population?

DLST p.Val49Ile (c.145G>A) is rare (popmax 0.369%, sas) (gnomAD).

What do computational predictors say about DLST p.Val49Ile (c.145G>A)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

DLST p.Val49Ile

c.145G>A · rs61755652 · VCV2741849

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.369%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.92	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 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.42	unconstrained · MANE · 7,336 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	21.3	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 0.369% South Asian · 336/90,954 alleles

Filtering AF 0.337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.324%

Overall 0.0623% 1,005/1,612,968 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.369%	271
Amishnot grpmax-eligible	0.329%	304
Middle Eastern	0.248%	404
Remaining individualsnot grpmax-eligible	0.0624%	1,601
European (non-Finnish)	0.0491%	2,037
Admixed American	0.0251%	3,991
African / African-American	0.0213%	4,687
Finnishnot grpmax-eligible	0.00313%	31,978

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.Val49Ile
Coding: c.145G>A
MANE Select: NM_001933
dbSNP: rs61755652
Type: single nucleotide variant
Location: chr14:74885633 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 77.40 · 2 PDB

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

Similar variants

DLST p.Ala264Val Uncertain significance ★★ ⚠ same type
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-val49ile (accessed [today's date]).

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