Is DLK2 p.Ser31= (c.93C>T) pathogenic?

DLK2 p.Ser31= (c.93C>T) is classified Likely benign in DLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Rare (popmax 0.985%, mid).

How common is DLK2 p.Ser31= (c.93C>T) in the general population?

DLK2 p.Ser31= (c.93C>T) is rare (popmax 0.985%, mid) (gnomAD).

DLK2 p.Ser31=

c.93C>T · rs34764062 · VCV2656603

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.985%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP 0.53, phastCons 1
Overall
CADD	11.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.985% Middle Eastern · 59/5,988 alleles

Filtering AF 0.944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.938%

Overall 0.833% 13,323/1,598,608 alleles · rare exomes 12,325/1,446,412 · genomes 998/152,196 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.2%	84
Finnishnot grpmax-eligible	1.12%	89
Middle Easterngrpmax	0.985%	101
European (non-Finnish)	0.959%	104
Remaining individualsnot grpmax-eligible	0.793%	126
Amishnot grpmax-eligible	0.548%	182
Admixed American	0.462%	217
African / African-American	0.155%	646
South Asian	0.0857%	1,167

Ashkenazi Jewish 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: DLK2
Protein: p.Ser31=
Coding: c.93C>T
MANE Select: NM_023932
dbSNP: rs34764062
Type: single nucleotide variant
Location: chr6:43454458 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 74.43
Residue 31: the egf-like 1 domain

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

Similar variants

DLK2 p.Ala19Thr Uncertain significance ★ ⚠ same type
DLK2 p.Ala19Val Uncertain significance ★ ⚠ same type
DLK2 p.Arg143Cys Uncertain significance ★ ⚠ same type
DLK2 p.Arg59His Uncertain significance ★ ⚠ same type
DLK2 p.Asp27Asn Uncertain significance ★ ⚠ same type
DLK2 p.Asp43Glu Uncertain significance ★ same type
DLK2 p.Cys117Tyr Uncertain significance ★ ⚠ same type
DLK2 p.Glu114Gly 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/dlk2-p-ser31 (accessed [today's date]).

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