Is DEPP1 p.Arg83Gln (c.248G>A) pathogenic?

DEPP1 p.Arg83Gln (c.248G>A) is classified Likely benign in DEPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-05). AlphaMissense: likely benign (0.0655); Ultra-rare (popmax 0.0166%, mid).

How common is DEPP1 p.Arg83Gln (c.248G>A) in the general population?

DEPP1 p.Arg83Gln (c.248G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DEPP1 p.Arg83Gln (c.248G>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

DEPP1 p.Arg83Gln

c.248G>A · rs149139243 · VCV3081757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -6.03	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 -2.5	GERP -3.1
Regional constraint	o/e 0.95	unconstrained · MANE · 635 bp · p 0.43 · regional, not allelic
Overall
CADD	0.227	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 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00212%

Overall 0.00487% 78/1,601,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.137%	729
Middle Easterngrpmax	0.0166%	6,014
Remaining individualsnot grpmax-eligible	0.0129%	7,723
Admixed American	0.0086%	11,629
South Asian	0.00442%	22,630
European (non-Finnish)	0.00171%	58,629

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: DEPP1
Protein: p.Arg83Gln
Coding: c.248G>A
MANE Select: NM_007021
dbSNP: rs149139243
Type: single nucleotide variant
Location: chr10:44977783 (GRCh38)
Gene constraint: LOEUF 1.774 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 60.32

Full DEPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEPP1 p.Thr101Ala Benign ★★ same type
DEPP1 p.His210Arg Uncertain significance ★ ⚠ same type
DEPP1 p.Ser183Phe Uncertain significance ★ ⚠ same type
DEPP1 p.Val9Met Uncertain significance ★ ⚠ same type
DEPP1 p.Arg88Cys 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/depp1-p-arg83gln (accessed [today's date]).

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