Is DERL2 p.Leu78= (c.234A>G) pathogenic?

DERL2 p.Leu78= (c.234A>G) is classified Likely benign in DERL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). Very rare (popmax 0.00739%, nfe).

How common is DERL2 p.Leu78= (c.234A>G) in the general population?

DERL2 p.Leu78= (c.234A>G) is very rare (popmax 0.00739%, nfe) (gnomAD).

DERL2 p.Leu78=

c.234A>G · VCV3501181

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00739%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor gain at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.9	GERP 0.74, phastCons 1
Overall
CADD	14.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00739% European (non-Finnish) · 87/1,177,286 alleles

Filtering AF 0.00606% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00566%

Overall 0.00571% 92/1,610,778 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00739%	13,532
African / African-American	0.00534%	18,713
Remaining individualsnot grpmax-eligible	0.0016%	62,380

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: DERL2
Protein: p.Leu78=
Coding: c.234A>G
MANE Select: NM_016041
Type: single nucleotide variant
Location: chr17:5481389 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 81.82

Full DERL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DERL2 p.Ala19Thr Uncertain significance ★ ⚠ same type
DERL2 p.Arg225Trp Uncertain significance ★ ⚠ same type
DERL2 p.Asn191Ser Uncertain significance ★ ⚠ same type
DERL2 p.Glu214Ala Uncertain significance ★ ⚠ same type
DERL2 p.Glu224Gly Uncertain significance ★ ⚠ same type
DERL2 p.Ile204Val Uncertain significance ★ ⚠ same type
DERL2 p.Leu237Val Uncertain significance ★ ⚠ same type
DERL2 p.Leu8Met 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/derl2-p-leu78 (accessed [today's date]).

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