Is DPEP3 p.Thr70Ala (c.208A>G) pathogenic?

DPEP3 p.Thr70Ala (c.208A>G) is classified Uncertain significance in DPEP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0682); Very rare (popmax 0.00661%, sas).

How common is DPEP3 p.Thr70Ala (c.208A>G) in the general population?

DPEP3 p.Thr70Ala (c.208A>G) is very rare (popmax 0.00661%, sas) (gnomAD).

What do computational predictors say about DPEP3 p.Thr70Ala (c.208A>G)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

DPEP3 p.Thr70Ala

c.208A>G · VCV3504853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00661%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.84	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 -0.14	GERP -1, phastCons 0.004
Regional constraint	o/e 0.88	unconstrained · MANE · 4,612 bp · p 0.0029 · regional, not allelic
Overall
CADD	6.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% South Asian · 6/90,826 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000548% 8/1,459,758 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00661%	15,138
Remaining individualsnot grpmax-eligible	0.0016%	62,370
European (non-Finnish)	8.48e-05%	1,179,092

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: DPEP3
Protein: p.Thr70Ala
Coding: c.208A>G
MANE Select: NM_001370198
Type: single nucleotide variant
Location: chr16:67980173 (GRCh38)
Gene constraint: LOEUF 1.097 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 2 PDB

Full DPEP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPEP3 c.-44A>T Uncertain significance ★ same type
DPEP3 c.-47C>G Uncertain significance ★ same type
DPEP3 c.-5G>T Uncertain significance ★ same type
DPEP3 c.-62C>T Uncertain significance ★ same type
DPEP3 c.-6C>T Uncertain significance ★ same type
DPEP3 p.Ala11Thr Uncertain significance ★ ⚠ same type
DPEP3 p.Ala157Pro Uncertain significance ★ ⚠ same type
DPEP3 p.Ala284Gly 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/dpep3-p-thr70ala (accessed [today's date]).

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