Is DEPP1 p.Thr101Ala (c.301A>G) pathogenic?

DEPP1 p.Thr101Ala (c.301A>G) is classified Benign in DEPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-03). AlphaMissense: likely benign (0.0637); Low-frequency (popmax 2.35%, afr).

How common is DEPP1 p.Thr101Ala (c.301A>G) in the general population?

DEPP1 p.Thr101Ala (c.301A>G) is low-frequency (popmax 2.35%, afr) (gnomAD).

What do computational predictors say about DEPP1 p.Thr101Ala (c.301A>G)?

AlphaMissense predicts likely benign (score 0.0637) — an in-silico prediction, not a clinical call.

DEPP1 p.Thr101Ala

c.301A>G · rs116781265 · VCV786154

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0637 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.35%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0637	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.18	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 -1.3	GERP -3.4
Regional constraint	o/e 0.95	unconstrained · MANE · 635 bp · p 0.43 · regional, not allelic
Overall
CADD	0.27	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 2.35% African / African-American · 1,762/74,858 alleles

Filtering AF 2.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.23%

Overall 0.137% 2,207/1,609,868 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.35%	42
Middle Eastern	0.68%	147
Admixed American	0.243%	412
Remaining individualsnot grpmax-eligible	0.23%	435
European (non-Finnish)	0.00934%	10,711
South Asian	0.0077%	12,995

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.Thr101Ala
Coding: c.301A>G
MANE Select: NM_007021
dbSNP: rs116781265
Type: single nucleotide variant
Location: chr10:44977730 (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.His210Arg Uncertain significance ★ ⚠ same type
DEPP1 p.Ser183Phe Uncertain significance ★ ⚠ same type
DEPP1 p.Val9Met 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-thr101ala (accessed [today's date]).

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