Is DEPP1 p.Val9Met (c.25G>A) pathogenic?

DEPP1 p.Val9Met (c.25G>A) is classified Uncertain significance in DEPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: ambiguous (0.5393); Ultra-rare (popmax 0.0165%, mid).

How common is DEPP1 p.Val9Met (c.25G>A) in the general population?

DEPP1 p.Val9Met (c.25G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DEPP1 p.Val9Met (c.25G>A)?

AlphaMissense predicts ambiguous (score 0.5393) — an in-silico prediction, not a clinical call.

DEPP1 p.Val9Met

c.25G>A · rs565312333 · VCV3081758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5393 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5393	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.64, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 635 bp · p 0.43 · regional, not allelic
Overall
CADD	23.7	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 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00112% 18/1,610,914 alleles · ultra-rare exomes 18/1,458,610 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
East Asian	0.00669%	14,952
South Asian	0.0055%	18,167
Admixed American	0.00507%	19,733
Remaining individualsnot grpmax-eligible	0.0016%	62,392
European (non-Finnish)	0.000424%	235,876

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.Val9Met
Coding: c.25G>A
MANE Select: NM_007021
dbSNP: rs565312333
Type: single nucleotide variant
Location: chr10:44978006 (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.Arg83Gln Likely benign ★ 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-val9met (accessed [today's date]).

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