Is DLK2 p.Asp261Val (c.782A>T) pathogenic?

DLK2 p.Asp261Val (c.782A>T) is classified Conflicting classifications of pathogenicity in DLK2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1495); Ultra-rare (popmax 0.0866%, afr).

How common is DLK2 p.Asp261Val (c.782A>T) in the general population?

DLK2 p.Asp261Val (c.782A>T) is ultra-rare (popmax 0.0866%, afr) (gnomAD).

What do computational predictors say about DLK2 p.Asp261Val (c.782A>T)?

AlphaMissense predicts likely benign (score 0.1495) — an in-silico prediction, not a clinical call.

DLK2 p.Asp261Val

c.782A>T · rs141543597 · VCV2656602

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1495 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0866%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1495	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -4.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.66	GERP -3.5, phastCons 0.023
Regional constraint	o/e 0.74	unconstrained · MANE · 4,283 bp · p 1.3e-09 · regional, not allelic
Overall
CADD	9.007	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 0.0866% African / African-American · 65/75,044 alleles

Filtering AF 0.0697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0636%

Overall 0.0148% 239/1,614,110 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0866%	1,155
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	0.0131%	7,613
Admixed American	0.01%	10,005

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: DLK2
Protein: p.Asp261Val
Coding: c.782A>T
MANE Select: NM_001198934 · reported on NM_023932
dbSNP: rs141543597
Type: single nucleotide variant
Location: chr6:43450909 (GRCh38)

Full DLK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dlk2-p-asp261val (accessed [today's date]).

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