Is ADGRD2 p.Leu112= (c.336G>A) pathogenic?

ADGRD2 p.Leu112= (c.336G>A) is classified Likely benign in ADGRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Rare (popmax 0.901%, mid).

How common is ADGRD2 p.Leu112= (c.336G>A) in the general population?

ADGRD2 p.Leu112= (c.336G>A) is rare (popmax 0.901%, mid) (gnomAD).

ADGRD2 p.Leu112=

c.336G>A · rs144326848 · VCV2659492

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.901%, 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 0.2	GERP -0.51, phastCons 0.85
Overall
CADD	3.929	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.901% Middle Eastern · 30/3,330 alleles

Filtering AF 0.648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.321% 2,168/675,756 alleles · rare exomes 1,719/523,438 · genomes 449/152,318 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.987%	101
Middle Easterngrpmax	0.901%	111
European (non-Finnish)	0.428%	233
Ashkenazi Jewishnot grpmax-eligible	0.409%	245
Remaining individualsnot grpmax-eligible	0.392%	255
Admixed American	0.36%	277
South Asian	0.116%	864
African / African-American	0.108%	923
Finnishnot grpmax-eligible	0.0478%	2,093
East Asian	0.0027%	36,988

Amish 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: ADGRD2
Protein: p.Leu112=
Coding: c.336G>A
MANE Select: NM_001395425
dbSNP: rs144326848
Type: single nucleotide variant
Location: chr9:124453057 (GRCh38)
Structure: AlphaFold pLDDT 72.98

Full ADGRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADGRD2 c.2669+3G>A Likely benign ★ 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/adgrd2-p-leu112 (accessed [today's date]).

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